Functional and Molecular Imaging
for Radiation Therapy Guidance
Imaging
3D modeling
Pt setup and
treatment delivery
Treatment planning
L Xing, T Li, Y Yang, E. Schreibmann, B Thorndyke, D. Spielman
3D/4D CBCT
4D imaging
Biological
imaging
Department of Radiation Oncology
4D planning
4D modeling
Stanford University School of Medicine
Adaptive therapy
(imaging, planning, delivery)
Gated tx planning
Day 0
Day 14
Day 24
PET/CT
Targeting in current radiation oncology
Intra-fraction organ movement, in particularly,
respiratory motion
Where is the tumor?
Inter-fraction organ movement
Target volume definition & localization
Pre-treatment staging & planning
Is tumor responding to therapy?
Anatomic
Imaging
• Tissue Characterization
and Classification
Molecular
Imaging
19 July 2000
18 July 2000
21 September 2000
21 August 2000
Treatment plan for prostate patient with nodal risk>15%
90%
100%
50%
• Staging
• Restaging
• Prognosis
Anterior Field
Lateral Field
Axial Field
Treatment plan for prostate patient with nodal risk <15%
• Monitoring Treatment
A. Quon
1
Where is the tumor?
Where is the boundary of the tumor?
Shortcomings of Current Radiation Therapy
• Staging and treatment decision-making are based largely on
anatomical imaging.
• Tumor volume defined on CT/MRI may often be too small or
too large.
• The whole Rx course takes 5-6 weeks and there is no effective
tools to distinguish responders from un-responders.
• Detection of recurrence is problematic.
What is the biology distribution?
• Spatial biology distribution is not considered.
Imaging
3D modeling
IMRT provides an unprecedented means to produce
customized 3D-dose distributions with sub-cm resolution.
Pt setup and
treatment delivery
Treatment planning
Integration of radiological imaging techniques allows better
patient positioning and dose delivery.
4D imaging
Biological
imaging
3D/4D CBCT
4D BCRT planning
Functional/metabolic imaging modalities are available for
noninvasively providing critical needed metabolic and
physiological data.
4D modeling
Adaptive therapy
(imaging, planning, delivery)
Day 0
Day 14
Molecular imaging techniques are emerging.
Day 24
The Current Imaging Toolbox
Method
Integration of biological and functional Image.
-- Biologically Conformal Radiation Therapy (BCRT)
Minimum Detectable
Size (φ
(φ)
Minimum Detected
Cells (n)
CT
1~2 mm
400,000
MRI
1~2 mm
400,000
MRSI
7 mm (~3mm at 3T)
1,000,000
SPECT
4~6 mm
600,000
PET
3~5 mm
400,000
HFUS
<1 mm
100,000
Optics
0.02 mm
1000
----to truly individualize radiation therapy
2
day4
day1
day8
Luciferase--Transcriptional Reporter
Bench-top Small Animal
Imaging System: Macroscope
hν
hν
ATP
ATP
Luciferin
Luciferin
Luciferase
Luciferase
ADP
ADP ++ Pi
Pi
Oxyluciferin
Oxyluciferin
2+
Mg
Mg2+
O
O22
Genome
Genome
Day11 after
inoculation
Fluorescence
Fluorescence
Excitation
P Maxim, S Gambhir, C Contag, and L Xing, Molecular Imaging.
Clinically available molecular/Functional
imaging tools
Project in Cellular & Molecular Imaging
Stanford University Medical Center (C. Contag)
ion
iss
m
E
Promoter
Promoter
Luciferase
Luciferase
Bioluminescence
Bioluminescence
Genome
Genome
ion
iss
Em
Substrate
& energy
Endorectal Coil-Based 3T MR Spectroscopic Imaging for Radiotherapy
3T Endorectal Probe
MR Spectroscopic Imaging (MRSI)
Functional MRI, DWI/DTI
MRSI: monitor the molecular properties of a tumor
ER Coil----high SNR MRI/MRSI
ER Coil----severely distorts the prostate
PET, SPECT
PET and PET/CT
Topic
Characterization of Tissue
Example
Solitary Pulmonary Nodules
Staging
Lung Cancer
Restaging/Prognosis
Lymphoma/Breast Cancer
Monitoring Treatment
GIST, Breast CA, Lymphoma
Emerging Applications
XRT planning
• Appropriate management decisions starts with accurate staging
• PET changes overall management in more than 30% of cases
Gambhir, et al 2001
Dizendorf et al, JNM 44, 24-29, 2003
3
Commonly used positron emitters
PET/CT for Radiation Therapy
• delineate target volume
• assess therapeutic response
• distinguish recurrent tumor and radiation necrosis
Pre-treatment
PET/CT/MRI
PET/CT/MRI-based
tumor delineation
Planning
& treatment
Post-treatment
PET/CT/MRI
Isotope
HalfHalf-life
(min.)
Production
method
Application Production
Cyclotron
Max. range
in water
(mm)
1.1
11C
20
13N
10
11C-Choline
11B(p,n)11C
Cyclotron
1.4
13N
ammonia
15O
13C(p,n)13N
2
Cyclotron
1.5
15O
water
18F
110
Cyclotron
1.0
FDG, FLT
68Ga
1.1 hr
Generator
1.7
82Rb
1.3
Generator
1.7
14N(d,n)15O
19F(p,pn)18F
18O(p,n) 18F
Registration
& analysis
FLT, 11C-choline, 18F-choline, Acetate, F-Dopa, Cu-ATSM, F-MISO, F-EF5…
Receptors and peptide-based tracers.
Proliferation imaging
Buck et al., J Nucl
Med, 2003
Post-treatment
Functional Image-Guided IMRT
• What needs to be done?
Reliable imaging tools.
Integration---network transfer of functional image files, file
format conversion, image fusion/deformable image registration….
Image fusion.
Inverse treatment planning.
Quality assurance .
Clinical study of the efficacy.
Pre-treatment
Post-treatment
4
A Liver Cancer patient
Example: 4D PET
Patient
setup
CTAC
(best at
expiration)
GE 4D PET
RPM
system
GE gated
PET
Recon
selected
gates
Stanford new 4D
PET technique
Conventional 3D PET
1 cm
4D
planning
If bin size = ∆t, then in each
respiratory cycle:
Bin 1 accumulates events from [0, ∆t]
Bin 2 accumulates events from [∆t, 2∆t]
Bin 3 accumulates events from [2∆t, 3∆t]
.
.
.
Bin N accumulates events from
[(N-1)∆t, N∆t]
3D PET --- the lesion in the ungated image is
elongated, and mislocalized superiorly by ~1 cm.
16
Ungated
Gated at Insp with 1.25 sec
Retro. Stacked at Insp
14
12
GET PET – location is right but signal is week.
CNR
10
8
R
N
C
6
4
2
RS 4D PET – location and signal are great☺.
0
-2
3D PET give wrong location and wrong volume
0
5
10
15
20
25
30
35
craniocaudal location (mm)
40
45
50
Functional Image-Guided IMRT
RS 4D PET imaging technique
sagittal
• What needs to be done?
coronal
Reliable imaging tools.
Image fusion.
Inverse treatment planning.
Quality assurance .
Stanford 4D PET image at end-inspiration. The lesion
has clearly emerged from the background activity at
the end-inspiration location.
(B. Thorndyke, E. Schreibmann, A. Koogn, and L. Xing, Med Phys, 2006).
Image Registration
Automated registration based on control volume(s).
CT images
Hardware Fusion
CT
scan
Raw
CT data
20 min timesaving
PET
scan
Scatter and
attenuation
correction
Raw
PET data
PET images
Schreibmann and Xing, Med. Phys., 2006.
~ 8 min per coach position
5
Head and neck
CT, PET, and IMRT
treatment plan
CT
PET
PET
CT
4D Image Registration
Deformable image registration
E. Schreibmann and L Xing, IJROBP, 2006
6
Functional Image-Guided IMRT
Biological image based inverse treatment planning
• What needs to be done?
3 SD
5 SD
7 SD
Reliable imaging tools.
Image fusion.
PET/MRI/MRSI
Post-scan data processing
Quantify metabolism
Inverse treatment planning.
Prescription
Quality assurance .
Beam orientation/profile optimization
Fine-tune regional doses
Plan review
Inverse planning
MLC leaf sequencing
Biologically Conformal Radiation Therapy
IMRT Plan Incorporating MRSI data
Biological
imaging
Spatial distribution of
biological parameters
Spatially nonuniform conformal
dose distribution
Target 3 (SD=3)
40%
SD=3
95%
SD=5
Target 2
(SD=5)
50%
SD=7
20%
Tissue
40%
Target 1
(SD=7)
Dose (Gy)
L. Xing et al, PMB 47, 3567-3578, 2002 .
Prescription for molecular/functional image guided IMRT
TCPi = exp[− ρ 0i vi exp(−α i Di + γ i ∆T )]
Di =
αr
1
1 α ρ 
Dr − (γ r − γ i )∆T − ln r 0 r 
αi
αi
α i  α i ρ 0i 
Functional Image-Guided IMRT
• What needs to be done?
Reliable imaging tools.
Image fusion.
Inverse treatment planning.
Quality assurance .
Yang Y and Xing L, Med. Phys. 2005.
7
Quality Assurance
Relationship between the Cho/NAA ratios of the calibration solutions
obtained at 9.4 T versus the calibration-solution-filled vials inside the
phantom obtained at 1.5 T using a 2D PRESS sequence.
S. Hunjan, D. Kim, A. Adalsteinsson, D. Spielman, L. Xing, IJROBP 57, 1159-1173, 2003
S. Hunjan, D. Kim, A. Adalsteinsson, D. Spielman, L. Xing, IJROBP 57, 1159-1173, 2003
4D PET Image Enhancement - Phantom Validation
Functional Image-Guided IMRT
3D PET
• What needs to be done?
Motion direction
Motion direction
4D PET (after postacquisition data
processing using our
new algorithm)
30
Image fusion.
Inverse treatment planning.
Quality assurance .
Ungated
Gated with 0.4 sec
Gated with 1.0 sec
Retro. Stacked
25
Reliable imaging tools.
CNR
20
R
N
C
Intensity profiles along the motion direction
15
10
0
-5
-10
A lot of research!
B. Thorndyke, E. Schreibmann, A.
Koong, L Xing, Med. Phys. 2006
5
0
10
20
30
40
50
superioinferior location (mm)
60
70
80
(B. Thorndyke, E. Schreibmann, A. Koogn, and L. Xing, IJROBP).
Summary
Functional/molecular imaging is emerging.
day1
day4
day8
Next Generation Radiation Therapy
Integration of functional & molecular imaging
Biologically Conformal IMRT
----to truly individualize Rx
Day11 after
inoculation
Reliable imaging tool, registration, inverse
planning, QA, research.
P Maxim, S Gambhir, C Contag, and L Xing, Molecular Imaging., 2004
8
ACKNOWLEDGEMENTS
Former postdocs- S. Hunjan， J. Lian, …
Clinical faculty – A. Koong, K. Goodman, Q. Le, S. Hancock, A. Quon …
Physicist – G. Luxton, T. Pawlicki, P. Maxim,….
Funding agency –
NIH (1R01 CA98523 & 1R01CA104205)
DOD (PC040282 )
9