Toward Integrated Laser-Driven Ion Accelerator

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Nov 15, 2013 (3 years and 11 months ago)

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1


Toward Integrated Laser
-
Driven I
on Accelerator
Systems at the Photo
-
Medical Research Center in
Japan


P.R. Bolton
1
, T. Hori
1
, H. Kiriyama
1
, M. Mori
1
, H. Sakaki
1
,

K. Sutherland
2
, M.
Suzuki
1
, J. Wu
3

and A. Yogo
1



1

Pho
to
-
Medical Research Center, Japan Atomic Energy Agency,
,



8
-
1
-
7 Umemidai Kizugawa
-
shi, Kyoto 619
-
0215 Japan


2
Hokkaido University, School of Medicine, Sapporo
-
shi Kita
-
ku Kita



12 Jo Nishi 5 Ch
ome, 060
-
0812 Japan


3

SLAC National Accelerator
Laboratory,
Stanford University,



Menlo Park, California

USA

Abstract


Goals

and early progress at the Photo
-
Medical
R
esearch Center

are
summarized
. Laser
-
driven ion beam radiotherapy can require compact repetition
-
rated
laser systems with peak powers approaching the PW level.
Laser development at PMRC
is outlined. Our parallel
experimental and simulation efforts

aimed at

the development

of
a prototy
pe ion beamline as an integrated laser
-
driven ion accelerator system
are

presented
. In addition
some of our first medical and radiobiological experimental
investigations
, proton
-
induced double strand breaking in human cancer cells and
simulations of optimu
m dose distributions for ocular melanoma
are discussed
.
Recommended components of a balanced and comprehensive PMRC agenda are given.

2


1.
Introduction


The case for ion beam radiotherapy continues to be
well
-
made
around the
world.
Globally t
he number of
proton treatment facilities (PTFs)
, including those under
de
velopment,

is

about

thirty
. Thousands of patients each year now rec
eive proton beam
radiotherapy for

treat
ment of

cancerous tumors
.
The well
-
known Bragg peak
phenomenon
enables

improved
depth loca
lization of deposited proton dose where the
depth of the so
-
called

Bragg peak


increases with the proton kinetic energy.

It was
highlight
ed by Wilson years ago that

adequate
dose localization can spare healthy tissue
that c
an surround a cancerous tumor [
1
].
This
is an
artifact of the
inverse
energy
dependen
ce of the proton
stopping power
in contrast to the

exponential dose reduction
(the exception being close to the surface) with
increasing
depth for x
-
ray photons.
Professor Abe has written “It is no exag
geration to say that the history of radiotherapy is
the history of struggling to improve the dose localization and cell killing
effects of
radiation” [2
]. Our flagship theme and main g
oal at the Photo
-
Medical Research Center
(PMRC) is to develop a compact

ion beam radiotherapy (IBRT) facility that is
laser
-
driven (L
-
IBRT).

In this

report the term ion is inclusive
of

protons. The Bragg
peak phenomenon
indicates

that shallower

(
more
superficial) tumors can be treated with
lower ion energy than deeper ones (
for example
,

the 40
-
60 MeV proton energy
3


requirement for ocular melanoma

[3]
).
A
small
tumor requires fewer protons to achieve
a given integrated dose level.
Our initial goal will then focus where possible on the
treatment of small and superficial tumors

(
in many case
s

early stage tumors)
.


PMRC was established in 2007 as a community
-
based, multidisciplinary
research and development hub
to

foster and promote

collaboration and cooperation with
industrial, academic, medical, institutional and government partn
ers aimed at
the
targeted innovation of

medical and relate
d photonics technologies. PMRC

is funded
by the Japan Atomic Energy Agency (JAEA


through the ‘Special Coordination Fund
(SCF) for Promoting Science and Technology as commissioned by the Japan Min
istry
of Education, Culture, Sports, Science and Technology (MEXT))

and also by its ten
funding
partners.


This proceedings report presents a brief summary of some of the important
activities at PMRC that are aimed at development of a prototype ion beamlin
e that is
compact and laser
-
driven for application to cancer radiotherapy (
an
L
-
IBRT

facility
).


2.
Laser Requirements for Ion Acceleration


The transverse normal sheath acceleration model
(typically applied to

thick
er

targets
)

has become well
-
known and is relevant up to intensities
near

10
21

W/cm
2
[4].
4


Also, f
or ultrashort pulse
s

and ultrathin foil targets
a theory of
coherent
ion acceleration
has been recently reported [5
]. Higher peak intensities (10
22
to 10
24

W/cm
2
) are
app
ropria
te to the radiation pressure (
laser piston) regime

[6
]. These models describe
charge separation driven by high
ly intense

(relativistic) laser
pulses
. To date most
experimental results can be characterized with the following ‘at

source’ features that are
can be well
-
predicted by the TNSA model because of the target thickness and laser
pulse durations used:



divergent, laminar proton spray:
large

angular

spread ~ 10 degrees or more


ultralow
emittance ~ 10
-
4

mm mrad

(transver
se)


high extraction field
: ~ TV/m level


high peak current: bunch charg
e ~ 1
-

100’s nC





short b
unch duratio
n ~ picoseconds


large
energy spread with a maximum value: s
pread

~ 100 %



intensity dependent cutoff value




significant background pa
rticles: electrons, other ions, x
-
rays…




At t
he J
-
KAREN facility of the Kansai Photon Science Institute (KPSI) we
5


have
recently reached

cutoff proton energies
near

7 MeV with 1.8 J (51 TW)
focused to
about 10
20

W/cm
2

onto a 2.5 micron stainless steel foil target.
In general experimental
observations to date make it clear that the acceleration of protons by lasers to cutoff
energies near 100 MeV will require that laser systems deliver peak powers in the
100’s TW to 1

PW range to targets. For a 100 fsec pulse duration this means pulse
energies of 10’s to 100 J delivered at a repetition
-
rate (~ 10 Hz
-

100 Hz) and focused to
intensities of order 10
21

W/cm
2
.
Peak power a
lone is not adequate.
Pulses need to be
‘clean’ in

the sense of
having very
high contrast (at least
~
10
-
10
) and s
table on a
shot
-
to
-
shot basis.
Finally, we insist, that to provide a laser
-
driven ion beam
rad
iotherapy (L
-
IBRT) facility which

is cheaper and
more
compact
than a conventional
IBRT facility (s
uch as a synchrotron
-
based one),
such a laser system also
must
be
compact
.

3.
Summary

of Laser Development at PMRC


The J
-
KAREN laser at the Kansai Photon Science Institute of JAEA,
(a
schematic of which is shown in figure 1)
, is used for PMRC studies of
ion yields in high
power and high intensity laser experiment
s. It is a
Ti:Sapphire
-
based double CPA
system with a two stage OPCPA preamplifier that precedes a series of highe
r power
multi
-
pass amplifiers
where the second one is cryogenically cooled
[7,8
].
The system
6


bandwidth is ca
pable of generating 30
-
40 fsec
compressed pulses with a contrast as
good as 10
-
10
.
Furthermore, this

has
recent
ly

been
improved.
A three
-
pass Ti:sapphire
booster amplifier has been added this year to the system which will enable ~

0.5 PW
operation (20 J in 38 fsec).
The booster

amplifier is pumped by ~ 60 J of second
harmonic emission from a Nd:glass laser for which the ir extraction efficiency is near
50 %. At this pump energy we anticipat
e one shot
approximately every
20 minutes.

The pump beam profile at the Ti:sapphire crystal of the booster amplifier is made
uniform with a diffractive optical element (homogenizer) by SILIOS Technologies

[9
].
With increased peak power from

J
-
KAREN

laser system we hope
to reach focused
irradiation levels
near

10
21

W/cm
2

on target
.


In collaboration with one of our PMRC partners

we
are
also
developing

a
more
compact (tabletop) solid state system

that is designed to

operate at a repetition rate up to
100 Hz (currently at 1
0 Hz) with laser diode pumping. This is a CPA configuration
with a BBO
-
based three stage OPCPA preamplifier (currently pumped with 532 nm
emiss
ion from a Nd:YAG laser) and an
Yb:YAG thin disk final amplifier (laser diode
pumped at 940nm)

[10]
. The system
starts with a broadb
and, diode pumped,
mode
-
locked Yb:YAG oscillator operating at
a central wavelength of 1030 nm at 38
mW of average power (0.47 nJ at 80 MHz).

The Yb:YAG material is known for its
7


low quantum defect which can significantly reduce thermal

loading and the emission
bandwidth is broad enough (with a quasi
-
flat
-
topped spectral pro
file) to support
compressed

femtosecond pulse of duration

(FWHM)
, 250
-

300 fsec
.


The OPCPA single pass gain is ~ 10
7

bringing the ir pulse energy to 6.5 mJ

as
a stretched seed for the thin disk power amplifier.

With diode pumping of the

Yb:YAG
disk we have reached 70 mJ (uncompressed). With the 10.8 nm bandwidth pulses
we
have demonstrated compression

to
a duration of about 230 fsec

(near transform limit).
W
e

aim

to reach

200 mJ
(uncompressed)
soon
which will repre
sent 0.6 TW of peak
power (
with a
70 %
compre
ssor e
fficiency
)
.


4.
Integrated Laser
-
Driven Ion Accelerator System (ILDIAS)


As
stated in section 2
, the ‘spray’ of ions driven from the target
rear
surface is
well
-
organized
and the
10
-
4

level
emittance
is

orders of magnitude lower than that of a
conven
tional accelerator ion source.
However

the
angular
divergence of this emission
and

the typically large ene
rgy spread are two
serious
challenges that mu
st be confronted
in the development of a laser
-
driven

ion beamline for cancer therapy. Ion emission
features (esp
ecially the energy spectrum, the
single bunch charge

and associated energy
efficiency
) are s
trongly dependent on the laser
pulse pa
rameters so
the ion beamline is
8


appropriately

considered as part of an integrated laser
-
driven ion accelerator syste
m
(ILDIAS). The ILDIAS concept brings

a systems approach to L
-
IBRT
development
where diagnostics and beam control
functions

are addressed i
n addition to

beamline
and
ion
optics designs
.
We necessarily include also the laser and the laser target (
the
photo
-
anode
ion source) development in the ILDIAS concept. The laser not only
accelerates ions but can provide synchronous probe pulses for beamline

diagnostics and
control
s
. So, in addition to laser development we must also develo
p clean ion beamlines
(without background
xrays, neutrons,
and other
unwanted ions) with adequate shielding,
focusing, collimation, steering, fast
-
shuttering,
instrumentatio
n and co
ntrol
s

for stability,
etc.
ILDIAS is therefore defined to include
all
ion ‘transport’
which we distinguish

from
the ion ‘delivery’ system.
I
on delivery is downstream of ion

transport and deals with the
patient/tumor specific aspects of the final be
am
delivery
to the pat
ient which includes a
gantry (where needed),
dosimetry,
final collimation,
spot
-
scanning and organ motion
tracking for example.


An i
nitial demonstration of 2 MeV proton focusing was made at PMRC by

Nishiuchi
-
san and co
-
workers [11
].

This effort was conducted at a 1 Hz repetition rate
using a moving polyimide tape target (of 12.5 micron thickness) and used a pair of
conventional permanent quadrupole magnets (that were designed for 0.5 MeV protons).
9


With the J
-
KAREN laser pulse focused

to intensities
up to 10
20

W/cm

2

(and a contrast
of 10
-
7

at ~100 psec
prior to the peak of the main pulse) onto the tape target

a broad
proton

spectrum with a 3 MeV cutoff was

generated. This was determined with an inline
time
-
of
-
flight spectrometer based on detection of p
roton
-
induced scintillation that was
positioned

about 1.9 meters from the tape target. CR
-
39 film tracks were used to
determined the +/
-

10 degree divergence
from the tape source and also in the focal plane
have verified focusing to a 3 mm x 8 mm spot loca
ted 650 mm from the tape target
.
Within the a 200 KeV energy spread centered at 2.4 MeV a single proton bunch
contain
ed
1.3 x 10
7

protons of which about 30 %
were estimated to reach the focal plane
according to a Monte Carlo simulation. The transmission of the PMQ pair relative to the
full

proton spectrum is only about
3 %.


In pa
rallel with these experimental
tests we have also been simulating beamline
transpo
rt
with candidate designs. Figure 2

illustrates
a

test beamline conceptual design
shown with a compact laser and embedded within
a simplified

gantry.
A
summary of
simulation
input parameters

is given here. The laser target/ ion source generates a 1 nC
prot
on bunch for each laser shot with an energy spread near 100 % , a beam divergence
of +/
-

5 degrees and a cut
-
off energy of 80 MeV. The beamline is designed for 55 MeV
protons such that the overall proton transmission (to the patient as shown in the figure)

10


is about 1.2 % and the transmitted ener
gy spread is only about 1.3 %.
The 55 MeV was
chosen with treatment of ocular melanoma in mind. Dose simulations for ocular
melanoma performed at Hokkaido University will be shown in section V (discussion
of integ
rated dose as well as laser pulse and bunch charge requirements associated with
the simulation will be included in this latter section).
With s
uch designs
most of the
laser
-
accelerated protons are still discarded

due to the large divergence and energy
spr
ead at
the source
. The effective laser
-
to
-
proton energy efficiency is then the product
of the laser
-
to
-
proton energy efficiency at the source (which can be
up to a
few %) and
the proton beam
line

transmission to the tumor.
This effective efficiency is then
of order
10
-
4

to 10
-
3
.
We can ultimately deliver more laser
-
accelerated protons to the tumor
(higher effective efficiency)
if the
at source
divergence and energy spread
can be
significantly reduced.

Consequently increasing the effective energy efficiency is a
challenge for targetry as much as
it is
for beamline optics.


ILDIAS development requires the sustained coordinated efforts of the medical,
laser, laser
-
plasma and accelerator communities over an

extended time. It is initially
limited by laser and target technology yet
must be
guided by
rigorous
medical
requirements. Repetition
-
rated targetry is a major challenge and is an integral part of
this systems approach. The target provides both the photo
-
anode and extraction field for
11


accelerating ions. Test beamline development with the ILDIAS concept
is consistent
with a

‘shakedown’ philosophy
in which we
seek

to
know

as quickly as possible wh
at

main technical challenges
and difficulties to expect
.


5
.
Medical Applications


The ILDIAS conceptual design and par
ameters discussed in section 4

are based
on the results of dose distribution simulations reported by Sutherland and co
-
workers
[3
]. The spread out Bragg peak (SOBP) is simulated by a weighted
summation of five
discrete central

values of proton beam energy.
In this work the diameter (few mm) and
energy spread (few percent) of an ideal pencil proton beam were varied
to obtain
optimally uniform dose distributions.
Simulated dose distributions in
the case of
ocular melanoma
reveal that the

sensitivity of
dose to surrounding tissue
(organs at risk


OAR)
to
proton
beam diameter a
nd energy spread

exceeds that of the tumor being
treated
. The required
proton energy spectrum for optimized dose distribut
ions span
s

40
to 60 MeV requiring a total of about 2 x 10
10

protons to reach an inte
grated dose of 55
Gy for a tumor mass near 750 mg.

This
integrated
dose level c
an

be obtained wit
h a
laser
-
driven proton source that delivers
10
6

protons per laser pulse
to

the tumor
at a 10
Hz repetition
-
rate extended over twenty fractions each of duration two minutes.
12


Spot
-
scanning requires precise control of
the
parameters of
a well
-
specified pencil
proton beam

such as energy, position and
integration time to a specified
spot dose level
.
The beam diameter and its lateral displacement in the scan will
also
determine the
minimally relevant tumor size.


There is interest in investigating the potential application of PET imaging using
radioactive i
sotopes in an autonomous
mode. Detection of gamma photons

following
positron emission from proton
-
induced short
-
lived isotopes such as
11
C
(decay half life
~ 20 minutes) and
15
O (decay half life ~ 2
minutes) would be implemented.
Some
preliminary
measurements have been conducted

at the Hyogo Ion Beam Medical Center
(HIBMC


a

PMRC partner) to characterize how
well the proton beam position could
be monitored using water

(ice)
,
l
ucite and polyethylene targets

[12]
.

The phantoms
were
irradiated with a 5 mm diameter proton beam of 80
MeV k
inetic energy to an integrated
proton number of order 10
10
(

~
5 minute proton irradiation time).

Spot
-
scanning was
also u
sed with ~ 2 mm beam spacings.
It is important to demonstrate that
an

autonomous PET technique can be used to measure proton dos
e distributions in small
tumors, with short

proton irra
diation times and with adequately short
PET scan times.
For example, it remains a challenge to obtain clear PET images following irradiation at
the reduced level of 10
9

protons.

13



With the same
moving
tape t
arget as described in section 4

proton
s

in the
energy range 0.8 to 2.4 MeV were used to irradiate
human cancer cells in vacuum [13
].
The proton yield was generated by a laser intensity of about 5 x 10
19

W/cm
2
on target
delivered at a 1 Hz repetition

rate. An integrated proton dose of 20 Gy was delivered to
the cells with 200 proton bun
ches of duration about 15 nsec
(one proton bunch per laser
pulse). At the cell site the proton irradiation level was estimated to be about 10
3
nsec
-
1

mm
-
1
. We demonstrated for the first time laser
-
driven
proton
-
induced double strand
breaking in human cancer cells (A549).


6
.
Closing Remarks


Because of its multidisciplinary nature PMRC is a multifaceted effort with its
own in
trinsic

complexity. It is important to pursue this mission with a balance of
multiple parallel paths or foci where the portion of effort and relative significance for
each path or focus will vary with time as our
program

mature
s
. The first path which is
immediat
ely critical is clearly the continued development of highest peak
power laser
systems
(such as J
-
KAREN) and
laser
-
plasma
experiments using them
to explore and
determine laser pulse, target and diagnostic requirements in the single shot mode. A
second paral
lel pat
h
,
also
immediately critical, is the development and application of a
14


more compact repetition
-
rated laser system
.
A

repetition
-
rated system can also be used
to ad
vance targetry where the repetition
-
rated feature is essential.
However, a
s targets
become more sophisticated the challenge of
10 Hz to 100 Hz operation increases
.


A third parallel path is the development of a
laser
-
driven
prototype ion
beamline that demonstrates medically

acceptable performance at a
clinical stage as a
step to
ward the L
-
IBRT clinical facility. This has been referred to as the integrated
laser
-
driven ion accelerator system or ILD
IAS in which we take a systems
approach
integrating the laser system
and targetry with ion beamline design
. This
part of the
beamline
is the ion transport line for which we must address ion optics (that are
tunable
as well as
unique to the high peak currents and divergence at the ion source), beam

diagnostics,

dosimetry
(with the required redundancies
)

and potential
beam controls
(i
nclud
ing the potential for laser control of
ion beam
parameters
an
d

fast shutter
capability). Toward
realizing

the medical prototype,
as an intermediate step, it is
important

develop

a
lower energy ‘test’ ion beamline as a focus for initial ILDIAS
developments
.
This is partially due to the fact
lower laser peak powers and therefore
proton energies will be available first.

Furthermore, a

test beamline can also serve a dual
use in supporting
a
medi
cal and nonmedical agenda for

science

and a
pplicati
ons at the
reduced ion energy.
This
path is also about maintaining
a ‘state
-
of
-
readiness’ for when
15


we
do
have
repetition
-
rated
laser pulses that can generate beams of protons with
adequately high
proton energies.
During this

shakedown process
we learn abou
t where
the main
technical cha
llenges are in this endeavour.
The ILDIAS path will become
increasing important in the PMRC program. In particular the compactness requirement
must be addressed with rigor following the demonstration of medically acceptable
pe
rformance
at

the higher energy
(
the
clinical medical
prototype
)
. The design of
downstream
beam delivery
components such as a gantry (if needed) and a spot
-
scanning
system (if needed) will depend critically on making the ion transport beamli
ne
‘optimally’ c
ompact through
appropriate engineering and design.



A fourth parallel path is the focus on medical/biological studies relevant to
laser
-
driven ion beams. This path is critical because we are guided by medical
requirements in all phases of PMRC. There are
many essential topics in this path that
must be pursued in a timely manner. For example, therapy ‘niche’ verification
is
to
be
determined by available i
on beam energy, flux and other performance capabilities.
The development of appropriate imaging techniq
ues must be medically guided toward
the ultimate goal of ‘image
-
guided’ therapy. It is well
-
known that ion beam irradiation
studies that focus on the dynamics of the short ion bunch are essential to determine
16


relative biological efficiency for single cell
s and tissue.
In the conventional
longer
bunch/pulse mode experimental comparisons are being made with protons, carb
on ions
and x
-
rays at the HIBMC

[14]
.
It is clear also that detailed quantitative evaluations are
needed with dose distribution simulations
, the unique role for positron emission
tomography (PET) for short irradiation fraction
s
with low doses and small tumors,
spot
-
scanning requirements
and treatment planning issues
in general.
As

importantly
this path provid
es the much needed channel for
‘bottom line’
medical guidance and
specification of performance requirements
for a ‘test’ beamline and ultimately for

the
clinical
L
-
IBRT facility.


Finally it is important to also establish as a fifth parallel path, a nonmedical
science and technology pat
h where we can achieve
mid
-
program
milestone successes
that mark our progress and support the case for the overall mission o
f developing an
L
-
IBRT facility while also developing a research and development hub

for advancing
photo
-
medical technology
.
For thi
s path lower energy ‘test’ ion beamline

development

can be important. It has

already
been
noted above
that identified

medical and
radio
biological studies can also be conducted on such a test beamline.


L
-
IBRT is still high risk and exploratory. As has been

shown in many other
technological fields over the past few decades, the ubiquitous laser will find
its
17


relevance in IBRT and so we must proceed along this provocative and ambitious trail.
Of the five parallel paths identified above it is ILDIAS (third pat
h) and the
medical/biological studies (fourth path) which represent critical ‘next ste
ps’ toward
L
-
IBRT development.
The paths that are critically immediate are the first two, the
development of adequate lasers and laser
-
plasma experiments using high peak
power
single shot and repetition
-
rated systems.
As we proceed in a parallel arrangement as
recommend
ed

here we must
also
be mindful

of
two ongoing global surveys: (i) ion yield
results (notably spectra and efficiencies) from other high power laser faciliti
es
around
the world
noting laser pulse
requirements
, diagnostics and target types used in relevant
best cases and (ii) an assessment of existing (often called classical or conventional)
IBRT facilities as well as those under development,
funded for future
development

and
newly proposed. The former survey clarifies latest progress
and capability
with ion
source develop
ment for L
-
IBRT and the latter

clarifies the state
-
of
-
the
-
art for IBRT
which we
must match and
which we aim to advance
.





18


ACKNOWLEDGEMENTS

This work was supported by the Special Coordination Fund (SCF) for Promoting
Science and Technology
as
commissioned by the Ministry of Education, Culture, Sports,
Science

and Technology (MEXT) of Japan and also by the funding partners of the
Photo
-
Medical
Research Center (PMRC).


References

[1]

R.R.

Wilson, Radiol. 47 (1946)

487.

[2]

M. Abe,

Proc. Japan. Acad. Ser B 83 (2007) 151.




[3]

K. Sutherland
, S. Miyajijma, H. Date, H. Shirato, M. Ishikawa, M. Murakami, M.
Yamagiwa, P.R. Bolton an
d T. Tajima,
Radiol. Phys.
and Technol
. in press (
2009)
.

[4]

S. C. Wilks, A.B. Langdon, T.E. Cowan, M. Roth, M. Singh, S. Hatchett, M.H.
Key, D. Pennington, A. MacKinnon and R.A. Snavely, Phys. of Plasma. 8
(2001) 542.

[5]

T. Tajima, D. Habs and X. Yan, Rev of Accel. Sci. and Tech. (RAST) 1

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21


Figure captions

Fig. 1.

Architecture of the J
-
KAREN laser at the Kansai Photon Science Institute



(KPSI)


Fig. 2.

Concept of a laser
-
accelerated double bend achromat ion transport line within

a gantry.




22










Figure 1








23









Figure 2