Biomed Imaging Interv J 2006; 2(1):e10
doi: 10.2349/biij.2.1.e10
© 2006 Biomedical Imaging and
Intervention Journal
 ORIGINAL
ARTICLE
Commissioning and evaluation of a new
commercial small rodent x-ray irradiator MK
Woo1, PhD, RA Nordal2,
MD, MSc, FRCPC
1 Departments of Radiation Oncology and Medical Biophysics,
Sunnybrook and Women’s College Health Sciences Centre,
University of Toronto, Canada
2 UAB Comprehensive Cancer Center, Birmingham, Alabama, United
States
ABSTRACT
An appropriate radiation
source is essential in studies of tissue response in animal
models. This paper reports on the evaluation and commissioning
of a new irradiator suitable for studies using small animals
or cell culture. The Faxitron is a 160-kVp x-ray machine that
was adapted from an x-ray imaging unit through modifications
to facilitate experimental irradiation. The x-ray unit is housed
in a shielded cabinet, and is configured to allow multiple irradiation
positions and a range of field sizes and dose rates. Use of
this machine for animal irradiation requires characterisation
of relevant dosimetry, and development of methodology for secondary
beam collimation and animal immobilisation. In addition, due
to the limitation of the irradiator, the optimal selection of
three characteristics of the x-ray beam is important. These
three characteristics, namely, the dose rate, the beam uniformity,
and the field size are inter-dependent and the selection of
a combination of these parameters is often a compromise and
is dependent on the application. Two different types of experiments
are selected to illustrate the applicability of the Faxitron.
The Faxitron could be useful for experimental animal irradiation
if the experimental design is carried out carefully to ensure
that accurate and uniform radiation is delivered.
Keywords: Animal irradiator; rodent irradiation; radiobiology;
radiation beam measurement
INTRODUCTION
Animal models are of key importance in experimental radiation
research, and accurate partial or whole body irradiation is
critical for many types of investigations [1-4].
For example, delivery of specific doses to tumours is necessary
in assessing tumour radiation response. Dose response curves
for late radiation injury are often quite steep, and thus inattention
to dosimetry can result in failure to reproduce expected effects
[5-6]. Animal irradiation
has been performed using appropriately collimated sealed source
radioisotope machines. However, there is increasing interest
in delivering organ-specific or whole body irradiation using
x-ray units. There are several advantages of the latter. Firstly,
facility-licensing requirements are much less stringent for
x-ray machines. In addition, although clinical cobalt units
have been used for animal irradiation, a dedicated radiation
unit for experimental work is usually necessary because infection
control practices within large animal facilities often preclude
the transfer of animals between the animal colony and a remotely
located irradiator. Other factors such as lower costs, smaller
irradiator footprint, and easier maintenance, also add to the
advantages of an x-ray unit.
The use of x-ray units does, however, present certain challenges.
A major challenge is the more complicated dosimetry resulting
from a lower beam energy and hence shallower penetration into
tissue, leading to the possibility of non-uniformity of delivered
dose [7]. While depth dose characteristics
of x-ray beams are improved at longer treatment distances, the
limited dose rate capabilities of these irradiators represent
another challenge when appropriate treatment distances are employed.
While radioisotope units have been available for some time,
there is limited experience with commercial x-ray irradiators,
and the question naturally arises as to whether x-ray irradiators
can replace an isotope irradiator for animal irradiation experiments.
This work reports on the design of irradiation conditions for
partial and whole body animal irradiation using the Faxitron
irradiator. This evaluation validates the suitability of the
Faxitron for laboratory rodent irradiation experiments, and
predicts its suitability for irradiation experiments using cell
culture and other systems.
MATERIALS AND METHODS
The Faxitron model CP160 (Faxitron X-Ray Corp., Wheeling, IL,
USA) is a commercially available x-ray tube machine that is
designed for animal irradiation. It was developed based on the
modification of the company’s existing line of imaging
machines. The unit contains an x-ray tube mounted on the ceiling
of a steel cabinet measuring 85 cm x 85 cm x 110 cm. The x-ray
tube has a filter holder beyond the exit window for placement
of additional filtration. For these experiments an added filtration
of 0.8 mm Al was used. Inside the cabinet, eight tray guide
positions accommodate a range of source-to-sample surface (SSD)
distances varying from 13 to 99 cm, with a maximum field size
coverage of 72 cm diameter. Additional guides can be affixed
to the plexiglass tray for positioning of an animal jig or specimen.
The unit can deliver x-rays at a maximum energy of 160 kVp and
at a current of 6.3 mA. Power, current, and time settings are
specified through a control panel on the front of the unit.
Programming of a pre-stored set of kVp, mA, and time settings
is possible. Timer settings are adjustable in increments of
0.1 minute. Localisation of the beam is achieved through alignment
markings on the sample tray. Detailed specifications can be
found at the website (http://www.faxitron.com).
Figure 1 is a photograph of the unit with a rat placed on the
tray.
[View this figure] |
Figure 1 Interior of Faxitron cabinet.
An anesthetised rat is placed on a tray mounted at
shelf position 7. The x-ray tube can be seen at the
top. |
|
Three characteristics of the radiation beam are important for
the requirements of the irradiation experiments. The first is
the dose rate of the radiation beam, which heavily affects the
amount of time required for the experiment. The second is the
field size of the beam, which could limit, perhaps, the number
of animals that could be simultaneously irradiated. The third
is the uniformity of the dose deposition, in the depth direction,
i.e., in the direction that the beam travels through the tissue.
In general, a uniform dose is desirable in the depth direction
of the tissue, so that when a deep-seated tumour receives the
required dose any normal tissue above it would not unnecessarily
get a much larger dose.
It would be most desirable to have an x-ray beam that can
deliver a uniform depth dose with a large field size and a high
dose rate. Unfortunately, these parameters are inter-related
so that usually increasing one parameter will compromise the
others. For example, the dose rate could be increased by moving
the specimen closer to the x-ray source (smaller source-to-surface
distance (SSD)). However, this would reduce the maximum field
size and also increase the dose non-uniformity in the depth
direction. The selection of the appropriate irradiation parameters
then depends heavily on the particular type of irradiation experiments,
subject to the capability of the beam characteristics of the
irradiator.
The Faxitron was then evaluated in the context of the above
concept by applying the unit to two types of experiments in
our laboratory. The first type is a small field irradiation
of a single animal, and the second is the whole body irradiation
of a group of animals, where the animals are either mice or
rats. An example of the first type of experiments is the irradiation
of a section of the spinal cord; for the purpose of studying
radiation-induced response [2,4]
and an example of the second type of experiments is the ablation
of bone marrow [1,3]. For
the small field irradiation experiments, the dose uniformity
across the target volume in the depth direction of the beam
is not a problem due to the small volume, but the depth of the
target from the surface might result in a large dose delivered
to the surface, especially if the SSD is small. Hence, a configuration
with a parallel-opposing pair of beams, similar to that in standard
radiation therapy, is used to obtain a uniform dose distribution
in the depth dimension. For the whole-body irradiation experiments,
the requirements are much more stringent. The field size has
to be large enough to cover the whole animal, and preferably
even larger to cover multiple animals. Moreover, the dose across
the whole body in the depth direction has to be uniform to within
10%. In addition, the irradiation time need to be kept as short
as possible to improve efficiency and to minimise the confinement
of the animals. Again, the parallel-opposing beam configuration
is used.
In the commissioning of the Faxitron, measurements of the
beam characteristics for the two types of experiments were carried
out in a phantom and these are reported below to demonstrate
the capability of the Faxitron for these experiments. The depth-dose
data for 3 different SSD’s (9, 19 and 33 cm respectively)
were measured using a Markus type parallel-plate ion-chamber
(PTW-Freiburg, Freiburg, Germany) overlaid with sheets of tissue
equivalent material (Solid WaterTM phantom material, Gammex
RMI, Middleton, WI, USA). The absolute dose was determined using
the AAPM TG-61 protocol using a cross-calibration procedure
with the orthovoltage machine in the clinic. These depth-dose
data were then used to calculate the dose uniformity across
an animal with a thickness of 2 cm and 3 cm if a pair of parallel-opposing
beams is used in an irradiation experiment.
In addition to the depth dose measurements, other physics measurements
were carried out. These include measuring the beam uniformity
in the cross-plane direction using film. Also, the stability
of the dose rate with respect to delivery duration was assessed
by running the beam continuously for an extended period of time
(20 minutes). Lastly, the radiation level around the unit was
surveyed using a Geiger counter.
In this paper only the measurements in phantom are reported.
In the actual animal irradiation experiment, the pair of parallel-opposing
beams would be delivered in two equal parts, with the second
half to be delivered after flipping the animal or animal holder
over. The animals used for the experiments are husbanded in
the animal facility of the Sunnybrook and Women’s College
Health Science Centre, which is a laboratory animal colony accredited
by the Canadian Council of Animal Care. All experimental protocols
involving animals were approved by the Animal Care Committee
of the Sunnybrook and Women’s College Health Science Centre.
The experiments will be reported in a separate paper, and the
present work will only discuss the physics aspects on the commissioning
of the Faxitron irradiation unit. An illustration of the Faxitron
unit, as well as the process of the irradiation experiment,
are included in the attached movie file (available for download
with the online version).
RESULTS
The measured depth dose curves are shown in Figure 2, for the
3 SSD’s of 9, 19 and 33 cm respectively. The data have
negligible error bars (repeat measurements produce values that
agree within less than 1%), and the curves have been fitted
to the data and smoothed. Using these depth dose data, the calculated
dose variation for a parallel-opposing pair of beams in the
depth dimension for a phantom is shown in Figure 3a (for a phantom
thickness of 2 cm) and Figure 3b (for a phantom thickness of
3 cm). For example, in Figure 3a, the dashed curve shows the
dose variation in the depth direction for a phantom of thickness
2 cm, for an SSD of 19 cm, relative to 100% at the centre (0.0
mm) of the phantom. The dose on the surface (-10 mm and 10 mm)
is around 107%. Similarly, the dotted line shows that the surface
dose for an SSD of 9 cm is very high, up to 120% relative to
the mid-point dose. The surface dose for an SSD of 33 cm is
about 101.5%, showing good dose uniformity throughout the depth
of the phantom. For the phantom thickness of 3 cm, in Figure
3b, the dose uniformity for the SSD of 19 cm is just over 10%,
while that for an SSD of 9 cm is as high as 35%.
The trade-off in the dose uniformity for increased SSD is
reflected in the decreased dose rate to the phantom. For an
SSD of 19 cm in the 3 cm phantom, the dose rate was determined
to be around 350 cGy/min. The corresponding dose rate for an
SSD of 9 cm was 1500 cGy/min and that for the SSD of 33 cm was
160 cGy/min.
[View this figure] |
Figure 2 Percent Depth Dose curves
for SSD = 9, 19 and 33 cm. The curves have been fitted
to the measured data and smoothed. The uncertainties
of the data are negligible. The curves have been normalised
to 100% on the surface. |
|
[View this figure] |
Figure 3 Dose variation in phantom
with thickness, d of (a) 2 cm and (b) 3 cm, respectively.
The curves have been normalised to 100% at the centre
of the phantom. |
|
For other physics measurements, firstly, the beam uniformity
in the cross-plane direction as determined using film shows
that the useful area of the beam was substantially less than
as indicated by the beam outline on the tray. For example, at
the SSD of 33 cm, the indicated beam diameter on the tray was
26 cm, whereas the useful part of the beam where the uniformity
was within 10% was confined to a diameter of 16 cm. Secondly,
the stability of the dose rate over time was determined to be
within 5% over a period of 20 minutes. And lastly, no detectable
radiation level above background was measured outside the cabinet.
DISCUSSION AND CONCLUSIONS
The above results show that the Faxitron could be configured
to provide acceptable dose uniformity across animals of typical
thicknesses of 2 or 3 cm, for both the small field and whole-body
irradiation experiments. For the small field experiments such
as investigation of spinal cord radiosensitivity, a typical
dose prescription is around 18 Gy, resulting in an irradiation
time of about 3 minutes per side (SSD=19cm). For the whole-body
experiment, a typical dose for bone-marrow ablation is 8 Gy,
resulting in an irradiation time of 2.5 minutes per side (SSD=33cm).
Only one single rat could be covered in the whole-body irradiation
at a time, but for smaller mice about 3 animals could be irradiated
at the same time.
The fact that the animal has to be turned over means that
the animal has to be immobilised or anesthetised. A significant
improvement then would be to install a second x-ray tube on
the bottom of the cabinet to provide a parallel-opposed pair,
which would additionally halve the required time.
The low energy of the beam and the resulting steep dose fall-off
need to be carefully considered when assessing the applicability
of the Faxitron for any irradiation experiment. One example
is the irradiation of cells in suspension, since the specimen
cannot be turned over to achieve a uniform dose distribution.
A solution in a flask is also a problem.
Basically, the Faxitron can be considered to be an ortho-voltage
x-ray unit and the dosimetry of it conforms to the AAPM protocol
for beams of this energy range [8]. With careful
experimental design, it can provide a solution as a cost-effective
irradiator with minimal radiation-protection concerns.
ACKNOWLEDGEMENT
The authors would like to acknowledge the support of Dr. Shun
Wong and the Department of Medical Physics, Toronto-Sunnybrook
Regional Cancer Centre.
REFERENCES
- Krause DS, Theise ND, Collector MI, et al. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 2001;105(3):369-77.
[ Medline ]
- Lo YC, McBride WH, Withers HR. The effect of single doses of radiation on mouse spinal cord. Int J Radiat Oncol Biol Phys 1992;22(1):57-63.
[ Medline ]
- Varadkar PA, Krishna M. Differential activation of kinases in ex vivo and in vivo irradiated mice lymphocytes. J Radiat Res (Tokyo) 2004;45(1):127-31.
[ Medline ]
- Wong CS, Minkin S, Hill RP. Linear-quadratic model underestimates sparing effect of small doses per fraction in rat spinal cord. Radiother Oncol 1992;23(3):176-84.
[ Medline ]
- Zoetelief J, Broerse JJ, Davies RW, et al. Protocol for X-ray dosimetry in radiobiology. Int J Radiat Biol 2001;77(7):817-35.
[ Medline ][ CrossRef ]
- Puite KJ, Agrawal MS, Broerse JJ, et al. Dosimetry intercomparison for partial body x-irradiation of rats. Phys Med Biol 1980;25(1):13-24.
[ Medline ]
- Jordan TJ. Central axis depth dose data for use in radiotherapy. Br J Radiol 1996;(Suppl. 25)5:62-109.
- Ma CM, Coffey CW, DeWerd LA, et al. AAPM protocol for 40-300 kV x-ray beam dosimetry in radiotherapy and radiobiology. Med Phys 2001;28(6):868-93.
[ Medline ]
APPENDIX
[View this
video] |
A video (.wmv, 4.75MB) showing the process of the
irradiation experiment |
Received 27 October 2005; received
in revised form 8 February 2006; accepted 28 February 2006
Correspondence: Department of Medical Physics,
Toronto-Sunnybrook Regional Cancer Centre, Toronto, Ontario,
Canada M4N 3M5. Tel.: (416) 480-5853; Fax: (416) 480-6801;
E-mail: milton.woo@sw.ca
(Milton Woo).
Please cite as: MK Woo, RA Nordal, Commissioning
and evaluation of a new commercial small rodent x-ray irradiator,
Biomed Imaging Interv J 2006;2(1):e10
<URL: http://www.biij.org/2006/1/e10/>
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