Lei Xing , Ph.D. & Jacob Haimson Professor
Department of Radiation Oncology & MIPS
Stanford University School of Medicine
……………………………
6/30/13
Case study – TrueBeam 6 MV FFF RapidArc Tx of a Lung SBRT
3D modeling
Pt setup and
treatment delivery
Treatment planning
Imaging
4D imaging
Biological
imaging
3D/4D CBCT
4D planning
4D modeling
Gated tx planning
Adaptive therapy
(imaging, planning, delivery)
6/30/13
6/30/13
Day 0
Day 14
Day 24
Head and neck
CT, PET, and IMRT treatment plan
Supine Craniospinal Irradiation with RA
Jianzhou Chen, Z. Chen, T. Atwood, I. Gibbs, S. Soltys, & L.
Xing, Supine Craniospinal Irradiation with VMAT to Improve Target
Dose Conformity and Homogeneity, JRO, 2012.
@01-258_via99-011_hepatoma_onscreen
1
sensitivity
Available Imaging Tools
O
im ptica
ag l
ing
XLCT
PET
SPECT
XFCT
MRSI
MRI
US
CT
Spatial
resolution
Radioluminescence & X-ray
Luminescence CT
CT Molecular Imaging using
nanophosphors
Principle
a
Optical radiation
Ionizing radiation
Current applications
-
PET and SPECT scintillators
-  CT detectors
-  Portal imaging
-
-  Dosimetry
Scintillation counting
-
High-energy physics
G. Pratx, 2012
Pratx, Sun, Carpenter & Xing, Optics Letters, 2011.
CT Molecular Imaging using QD and
nanophosphors
QD710-RGD peptide
A
h
E
B
C
D
F
a a
b
c
d
6/30/13
QD705
b
Modification of QD710-Dendron with a dimeric RGD peptide, RGD2. B: Excellent
solubility and monodisperity in aqueous solution for the QD710-Dendron (left) and
QD710-RGD2 (right). C: TEM image of QD710-RGD2. D: UV absorbance and NIRF
of the QD710-Dendron (bottom) and QD710-RGD2 (top). In vivo NIRF imaging of
QD710-RGD2 (active targeting, E) and QD710-Dendron (passive targeting, F) in
mice bearing SKOV3 tumor (Cheng’s lab).
QD800
@01-258_via99-011_hepatoma_onscreen
2
b
a
Photon yield vs dose
d
0.25
0.1
LaO2:Eu
e
0.5
0.3 pM
0.75
1
2 µg/mL
Gd2O2S:Eu
White light
Phos
in
Agar
Phos
Luminescence
Tissue-mimicking
material
c
f
Varian 100keV
fluoro
1 cGy
g
10 cGy
100 cGy
The white light image (a) and luminescence image (b) of the nanophosphor phantom. (c) X-ray luminescence
spectrum
of Gd2O2S:Eu. The Gd2O2S:Eu phantoms with different concentrations (d) and their X-ray
6/30/13
luminescence images under different X-ray irradiation dose 1 cGy (e), 10 cGy (f) and 100 cGy (g).
Multiplexing
X-ray induced optical luminescence images
ssDNA-Agx
Lysozyme-Au8
BSA-Au25
8
Int.
6
Blank
(a) Schematic of the locations of each type of RLNP. The inactive particles are indicated with the abbreviation (Ctrl).
(b,c) 6/30/13
The unmixed signal from the BaYF4:Tb and BaYF4:Eu particles, respectively. (d) The unmixed multiplexed image
with colorbars for the relative concentrations of BaYF4:Tb and BaYF4:Eu. (C. Carpenter et! al, 2012)
4.
1.
2.
3.
Water ssDNAssDNA LyzLyz BSABSA
Agx
Au8 Au25
4
2
0
1
2
3
4
1
!
X-ray induced optical luminescence intensities
Gultathione
Au18??
Gultathione-Au
Or
polymer-Au ion complex
60
Int.
40
Blank
1.
2.
3.
Water solution solid
20
0
1
2
3
3
@01-258_via99-011_hepatoma_onscreen
3
X-ray Luminescence Tomography
1% Agar 99% water
TiO2 for optical sctter
Ink for optical absorption
100 µM phosphor
G. Pratx et al, IEEE Trans. Med. Ima., 2010
1cm phosphor plug
6/30/13
Reconstruction: ML-EM
Noise from counting statistics:
Molecular sensitivity = 0.3 pM @ 1cGy
0.3 pM
Yi ~ Poisson(yi)
0.5
Log-likelihood:
0.75
10 cGy
1 cGy
0.25
Optimization:
1
0.1
2 µg/mL
Expectation-Maximization:
Tissue-mimicking
6/30/13
material
6/30/13
100 cGy
@.4<,<487E05/;
Spatially Encoded Light Emission
X-ray Luminescence Tomography
6/30/13
C. Carpenter et al, PMB 2012
@01-258_via99-011_hepatoma_onscreen
4
Reconstruction & linearity
Spatial resolution ~ 1 mm
50 radial positions
1.5
1
5
10 mg/mL
1
Phantom
2
3
4 mm
100 radial positions
0.5
64 angles
Offset (background)
128 angles
6/30/13
Reconstructed image (ML-EM)
Sinogram
Simulation vs Experiment
10 mg/mL
5 mg/mL
Reconstructed image
Simulation
Sinogram
Experiment
1 mg/mL
6/30/13
X-ray Fluorescence Molecular CT Imaging
6/30/13
X-ray Fluorescence Molecular CT Imaging
XFCT
CT
Sinograms (top) and reconstructed CT images (bottom) for XFCT (left) and
transmission CT (right) of the low-resolution phantom loaded with gold for a
0.1 mGy imaging dose. (Magda Bozalova et al)
M. Balazova, Y. Kuang, G. Pratx, L. Xing, X-ray Fluorescence Molecular CT Imaging, IEEE Trans Med Ima., 2012
M. Balazova, Y. Kuang, G. Pratx, L. Xing, X-ray Fluorescence Molecular CT Imaging, IEEE Trans Med Ima., 2012
@01-258_via99-011_hepatoma_onscreen
5
X-ray Fluorescence Molecular CT Imaging
X-ray Fluorescence Molecular CT Imaging
M. Balazova, Y. Kuang, G. Pratx, L. Xing, X-ray Fluorescence Molecular CT Imaging, IEEE Trans Med Ima., 2012
Au
Pt
Fig. 1. (left) Proposed XFCT/CT
system. (top) Physical mechanism of
X-ray fluorescence from K-shell
electrons.
6/30/13
6/30/13
K. Yu et al, AAPM 2012 (best paper in imaging)
Medical Physics Letters, 2013.
Multiplexing
K. Yu et al, AAPM 2012 (best paper in imaging)
Medical Physics Letters, 2013.
Multiplexing
6/30/13
K. Yu et al, AAPM 2012 (best paper in imaging)
Medical Physics Letters, 2013.
Overcoming Compton Scatter
Moiz Ahmad et al, Order of Magnitude Sensitivity Increase in X-ray Fluorescence CT (XFCT)
Imaging With an Optimized Spectro;9,<4,50<0.<8:87E2=:,<487!0/Ima, 2013
@01-258_via99-011_hepatoma_onscreen
6
Going Beyond K-Schell Imaging
High-sensitivity x-ray fluorescence CT
imaging of Cisplatin with L-shell x-rays
Magda ML-EM
Bazalova
et al,
ML-EM (w/o correction)
(w correction)
FBP
to be published
Magda Bazalova, to be published, 2013
80 keV
30 keV
15 keV
CT
Figure 2: CT images (first column, W/L = 800/0) and XFCT images reconstructed with filtered backprojection (FBP, second column) and maximum likelihood expectation maximization (ML-EM, 20
High-sensitivity x-ray fluorescence CT
imaging of Cisplatin with L-shell x-rays
X-ray acoustic tomography (XACT) with pulsed
!
X-ray
beam from a medical linear accelerator
Guillem Pratx, Yu Kuang, and Lei Xing
Liangzhong Xiang, Bin Han, Colin Carpenter,
Figure 5: Profiles along a horizontal (left) and vertical (right) line across the phantom for the 15 keV
images reconstructed with FBP (green), ML-EM without (blue) and with (red) attenuation correction.The
actual profile is marked by the black dashed line. The accuracy of concentration reconstruction is
significantly increased when attenuation correction is applied.
!
30 picoseconds per pulse
!
Xiang L et al, Medical Physics Letters, 2013
D  Interaction of X-ay with endogenous or exogenous
media provides the basis for X-ray molecular
imaging.
D  4235A;07;4<4>0,7/;90.4E.):,A6850.=5,:
imaging is possible.
D  XFCT, XLCT and XACT are a few examples of
X-ray molecular/physiological imaging that are
being developed at Stanford. @01-258_via99-011_hepatoma_onscreen
7