1. INSTITUTE OF PHYSICS PUBLISHING PHYSICS IN MEDICINE AND BIOLOGY
Phys. Med. Biol. 49 (2004) 3725–3735 PII: S0031-9155(04)81398-8
A state-of-the-art epithermal neutron irradiation
facility for neutron capture therapy
K J Riley1, P J Binns1 and O K Harling2
1 Nuclear Reactor Laboratory, Massachusetts Institute of Technology, 138 Albany St.,
Cambridge, MA 02139 USA
2 Department of Nuclear Engineering, Massachusetts Institute of Technology, 138 Albany St.,
Cambridge, MA 02139 USA
E-mail: flavor@mit.edu
Received 1 June 2004
Published 2 August 2004
Online at stacks.iop.org/PMB/49/3725
doi:10.1088/0031-9155/49/16/018
Abstract
At the Massachusetts Institute of Technology (MIT) the first fission converter-
based epithermal neutron beam (FCB) has proven suitable for use in clinical
trials of boron neutron capture therapy (BNCT). The modern facility provides
a high intensity beam together with low levels of contamination that is ideally
suited for use with future, more selective boron delivery agents. Prescriptions
for normal tissue tolerance doses consist of 2 or 3 fields lasting less than 10 min
each with the currently available beam intensity, that are administered with an
automated beam monitoring and control system to help ensure safety of the
patient and staff alike. A quality assurance program ensures proper functioning
of all instrumentation and safety interlocks as well as constancy of beam
output relative to routine calibrations. Beam line shutters and the medical
room walls provide sufficient shielding to enable access and use of the facility
without affecting other experiments or normal operation of the multipurpose
research reactor at MIT. Medical expertise and a large population in the greater
Boston area are situated conveniently close to the university, which operates the
research reactor 24 h a day for approximately 300 days per year. The operational
characteristics of the facility closely match those established for conventional
radiotherapy, which together with a near optimum beam performance ensure
that the FCB is capable of determining whether the radiobiological promise of
NCT can be realized in routine practice.
1. Introduction
The first attempt at treating cancers with boron neutron capture therapy (BNCT) was initiated
in 1951 (Slatkin 1991) using beams of thermal neutrons. Information about the potential
0031-9155/04/163725+11$30.00 © 2004 IOP Publishing Ltd Printed in the UK 3725

2. 3726 K J Riley et al
therapeutic effects of neutron capture in boron was emerging at that time and seemed to merit
clinical investigation despite an incomplete understanding of the complex radiobiological
processes that make BNCT so potentially attractive as a modality. The pioneering clinical
work of Sweet and colleagues ended when it became clear no therapeutic benefit was being
observed and, worse, in some cases excessive damage to superficial normal tissues was being
produced (Sweet 1997). BNCT was not tried again in the US until 1994 when separate
groups at the Massachusetts Institute of Technology (MIT) and Brookhaven National
Laboratory commenced studies for glioblastoma multiforme and subcutaneous melanoma.
In the intervening years a rationale for BNCT had become apparent that was based on
the preferential accumulation of boron in these tumours using boronated phenylalanine
(BPA) (Mallesch et al 1994, Coderre et al 1998). Important technological advances had also
occurred to allow rapid assay of specimens containing boron by prompt gamma neutron
activation analysis (PGNAA) and more importantly the design and construction of epithermal
(0.5 eV–10 keV) neutron beams that would avoid excessive skin dose and provide a therapeutic
effect on deep-seated tumours. Interest in BNCT was renewed and facilities around the world
soon launched Phase I clinical studies to determine the maximum tolerable dose using these
epithermal beams in conjunction with new boron compounds (Chanana et al 1999, Busse et al
2003).
The use of research reactors was the only pragmatic solution to provide a reliable
and intense source of neutrons suitable for NCT although their design was not necessarily
compatible for producing an optimum beam of sufficient intensity and purity. Many BNCT
facilities have low beam intensities that result in protracted irradiations, higher levels of
contamination causing unnecessary damage to healthy tissue that degrade treatment plans
or poor physical designs that constrain field placement. These shortcomings, although
a serious impediment, have so far not greatly hindered BNCT because the trials to date
have simply focused on normal tissue tolerance and not efficacy or tumour control. BNCT
still requires optimization of the complex biological and physical factors that distinguish
it from conventional radiotherapy and that will only be possible after Phase II clinical
investigations.
The fission converter concept is employed for the first time to provide a second-generation
epithermal neutron beam that is nearly optimum for clinical trials and successfully overcomes
the difficulties of extracting a suitable beam from the reactor core. The facility (FCB) complies
with all of the envisioned requirements for rigorous clinical evaluation of BNCT (Harling et al
2002a, Riley et al 2003) and is housed in the experimental hall of the MIT Research Reactor
(MITR-II). The reactor is located in metropolitan Boston with several teaching hospitals
nearby in the densely populated New England region of the US. Patients are admitted to the
hospital and travel to the reactor by ambulance for part of the day to receive irradiations and
then return to the clinic for 2–3 days of in-patient care and follow-up. The multipurpose
MITR-II operates at a maximum of 5 MW, 24 h a day for approximately 300 days per year
and the FCB runs independently of other experiments and does not interfere with other reactor
applications. The FCB provides a high purity, high intensity beam that enables irradiations
to average whole brain tolerance in approximately 25 min using boron compounds currently
approved by the Food and Drug Administration (FDA). The facility is augmented by the
PGNAA (Riley and Harling 1998) on a separate beam line in the reactor hall to enable rapid
assay of the boron content in biological specimens from the patient that is necessary to adjust
beam delivery to achieve the specified treatment plan (Kiger et al 2003) with a precision
better than 2%. Together these facilities are used in the current clinical trials for glioblastoma
multiforme and intracranial as well as metastatic melanoma and are the only facilities licenced
for BNCT in the US.

3. A state-of-the-art epithermal neutron irradiation facility for neutron capture therapy 3727
Figure 1. Plan view of the MIT epithermal neutron fission converter facility.
2. Facility description
The fission converter is designed and licenced to operate at 250 kW and is presently configured
to produce 83 kW by using only 10 partially burned fuel elements cooled with D2O. A shielded
horizontal beam line 2.5 m long directs neutrons from the converter to the treatment room as
shown schematically in figure 1. The beam line consists of a series of Al (81 cm), Teflon R
(13 cm) and Cd (0.5 mm) neutron filter/moderators, a lead photon shield (8 cm), and a large
conical collimator 1.1 m long with lead walls 15 cm thick. The 0.42 m long patient collimator
is made from a mixture of lead and boron or lithium (95% enriched in 6Li) loaded epoxy that
extends the beam line into the shielded medical room.
The neutron beam is controlled by three in-line shutters acting independently that are
installed along the length of the beam line. The first of these, starting near the reactor core is
the converter control shutter (CCS) that is a 0.5 mm layer of Cd followed by a 6.4 mm sheet
of aluminium alloyed with boron of natural isotopic abundance. This shutter modulates the
fission rate in the converter (and beam intensity) between 1 and 100% by shielding the converter
fuel against thermal neutrons incident from the MITR-II reflector region. Downstream from
the fuel is a 68 cm long tank that when filled with light water provides effective neutron
attenuation. Following this is the mechanical shutter that turns the beam on and off within 3 s
during therapy and comprises a large sliding slab to fill a section of the collimator with a
20 cm thickness of borated (100 mg cm−3 10B) high density (ρ = 4.0 g cm−3) concrete and
20 cm of lead.
The medical room is built with 1.1 m thick walls of high density concrete with a roof
of 15 cm thick steel beneath 55 cm of high density concrete. The wall of the medical room
nearest the FCB control console includes a window containing layers of quartz and lead glass
as well as mineral oil. Inner surfaces of the walls and ceiling are lined with 2.5 cm of borated
polyethylene to absorb thermal neutrons and reduce activation of the steel reinforced concrete
walls.
The beam centreline in the medical room is 0.42 m above the floor and the patient
collimator can be readily configured to provide aperture diameters of 80, 100, 120 and 160 mm

4. 3728 K J Riley et al
Figure 2. Setup for a lateral brain irradiation using the patient collimator (1) with the 120 mm
diameter aperture (2). Clinical staff monitor the patients and their vital signs (3) during an
irradiation through the shielded viewing window (4) and closed circuit cameras (5).
that conveniently extend up to 0.42 m beyond the wall of the medical room. The collimator
diameter tapers from 0.67 m at its base to 0.3 m near the patient that combines with ample
(14 m2) floor space in the medical room to allow patients to be comfortably positioned for
cranial irradiations in a full 180◦ arc around the beam centreline while lying supine on the
treatment couch. A photograph of a patient setup for a lateral brain irradiation is shown
in figure 2. A laser projection illuminates the central axis of the beam to help with patient
positioning as well as optics that penetrate the wall of the collimator to provide a beam’s eye
view. Prior to commencing an irradiation, the laser and optics are withdrawn and replaced
with a plug that has a composition identical to the collimator walls.
Four fission counters positioned in the periphery of the beam near the base of the patient
collimator serve as integral monitors of the neutron fluence as it is delivered to the patient.
Signals are fed to NIM electronics and irradiations are administered with a programmable logic
controlled (PLC) system that automatically terminates the irradiation when the integrated
counts on any of the four beam monitors first reach the prescribed targets. Data from
instrumentation in the FCB cooling system and beam line shutters are also fed to the PLCs,
which are programmed with automated interlocks to help ensure the safety of the patient and
operational staff alike. The facility is operated from the control console shown in figure 3
that includes a dedicated computer for displaying progress of an irradiation and archiving
data from the PLCs. During an irradiation the patient and their vital signs are monitored
through the shielded viewing window and closed-circuit cameras which contain an integrated

5. A state-of-the-art epithermal neutron irradiation facility for neutron capture therapy 3729
Figure 3. The FCB control console is equipped with two redundant PLCs (1) that automatically
control an irradiation. Signals from the four beam monitors are processed in NIM electronics
(2), fed to the PLCs then stored and displayed on a computer (3). The console is equipped with
closed-circuit television monitors (4) and is situated near the shielded window (5) so that patients
can be easily viewed throughout the course of an irradiation.
Key switch on
Enter beam Satisfy safety
monitor targets interlocks Medical room door closed
Power for shutter systems
BEV laser removed
Open shutters
Reset NO
Interlocks OK?
YES
Log data Beam Monitors less
than targets? NO
(every 10 ms) monitors
YES
Operator
intervene
SCRAM
YES
NO Over targets?
Close shutters
(> 102%)
Figure 4. Logic diagram of the FCB control system.
audio system for two-way communication between the medical room and control console.
The control system, medical room and support for the patient at the FCB are designed to
function as similarly as possible to conventional radiotherapy facilities in terms of safety and
convenience.
3. Beam monitoring and control system
3.1. Overview
The control logic during a patient irradiation is depicted in figure 4. Prior to commencing an
irradiation, a series of safety interlocks must be satisfied before the shutters can be opened to
turn the beam on. The prescribed monitor units are adjusted based upon PGNAA measurements
of the boron concentration in blood samples taken prior to irradiation and are entered using a
numeric keypad on the console. To prevent input errors, the system only accepts the entered

6. 3730 K J Riley et al
beam monitor counts after matching values for each channel are keyed in twice. The operator
commences therapy with a single pushbutton and the PLCs issue commands to open each
shutter in sequence and initiate data acquisition. It takes two minutes for all shutters to open,
and monitor counts accumulate continuously on the updated display. The PLCs repeatedly
interrogate all safety interlocks, check that the accumulated monitor counts are below the pre-
set targets and store the data from that interval in the computer. Like conventional radiotherapy
machines no other actions are required from the operator unless they need to intervene, for
which there is a manual override that terminates an irradiation by closing shutters or scramming
the reactor. When the accumulated counts on any one of the four beam monitors first reaches
the set target, the PLCs signal all shutters to close. To defend against overexposures that might
be caused by some mechanical or electrical failure during shutter closure, programmed safety
interlocks automatically scram the reactor if any channel exceeds 102% of the prescribed
target value.
Controls for opening shutters are deactivated when the shield door to the medical room is
open to help prevent inadvertent beam exposure of staff inside the room. Additional shutter
closure controls mounted inside the room are always active. If radiation levels inside the room
exceed 0.5 mSv h−1 an audible alarm warns personnel upon opening the door. The entrance
to the medical room is equipped with motion sensors that stop sideways movement of the
pneumatically operated 11 ton shielding door if anyone is in the vicinity and pressure sensitive
strips run along its leading edge to stop the door upon any contact.
Loss of building power would automatically scram the MITR-II, but if electrical power
fails only to the medical area, uninterruptible power supplies keep the PLCs, computer and
other vital instrumentation running for at least 20 min to enable an irradiation field to be
completed as planned. The mechanical shutter can be rapidly closed using a hand crank
located on the outside of the room while the water shutter and CCS close under the force
of gravity. The shielding door can also be opened by hand in an emergency to quickly gain
access to the medical room.
3.2. Performance
Seven clinical irradiations have so far been completed using the FCB without experiencing
any unexpected difficulties except for one reactor scram that was unrelated to operating the
medical facility and resulted in only a 1 h delay in giving the next radiation field. Average
whole brain doses of either 7.0 or 7.7 (RBE) Gy were delivered, with total irradiation times that
ranged from 25 to 79 min. Clinical irradiations commenced with the converter operating at
approximately 30 kW, which resulted in proportionately longer irradiations. Treatment plans
consisted of two or three fields that each lasted between 2 and 15 min and were delivered on two
consecutive days. Each of the 36 separate fields administered using the FCB were delivered
to within 1.5% of the prescribed targets, averaged over the four beam monitors (Kiger et al
2004), with 33 (92%) and 21 (58%) fields delivered to within 1 and 0.5%, respectively.
4. Health physics surveys
Photon and neutron dose equivalent rates were determined using Geiger–M¨ ller and tissue
u
equivalent proportional counter based survey instruments, respectively. With the reactor
operating at 4.5 MW, measurements were performed inside the medical room with the shutters
closed and outside the room with the shutters open (FCB operating at 76 kW) and scaled to
maximum operating levels (reactor power of 5 MW, converter power of 83 kW). The dose
equivalent rates outside the medical room contained no significant neutron contribution with

7. A state-of-the-art epithermal neutron irradiation facility for neutron capture therapy 3731
Table 1. Summary of the quality assurance programme for radiotherapy at the MIT FCB.
Surveillance Interval Criteria
Functional checks
Safety interlocks Monthly Functional
Alarm setpoints Each use Functional, set according to TS
Controls Each patient Functional
Equipment Each patient Functional
Output/constancy checks
Area radiation monitors Each patient Alarm operational
Beam monitors (voltage and Semi-annual Set point stable within 10%
discriminator plateaux)
Boron analysis system Each patient Constant within 10%
Ionization chambers, electrometer Each use Constant within 3%
Neutron beam Each patient Constant within 10%
Calibrations
Area radiation monitors Annual 10% accuracy
Boron analysis system Semi-annual 5% accuracy
Detector efficiency (gold foils) Semi-annual 3% accuracy
FCB power monitors Annual –
Ionization chambers, electrometer Bi-annual National standard, 1% precision
Neutron beam depth dose profile Semi-annual (each –
beam configuration)
a maximum of 12 µSv h−1 measured behind the rear wall opposite the beam. Since the
observed values are only marginally higher than the nominal background of approximately
8 µSv h−1 in the reactor hall without the converter operating, no additional access control to
the experimental hall is required when the FCB is in use.
Inside the medical room a dose equivalent rate of 200–300 µSv h−1 is apparent at the
patient position immediately following a 10 min irradiation that is due entirely to photons
emanating from the beam line. Approximately half of this activity arises from relatively short-
lived activation products (28Al, 56Mn and short-lived isomers of 122Sb and 124Sb) produced in
the patient collimator and after 12 h the dose equivalent rate is decreased to 100 µSv h−1.
This is higher than the 26 µSv h−1 associated with beam transmission through the closed
shutters that was first measured before any use of the facility and is attributed to a small build
up of residual activity in the patient collimator during its lifetime. General area dose rates of
approximately 20 µSv h−1 are observed away from the patient collimator in the medical room
with the reactor at full power and staff can therefore freely enter the room without the need to
lower reactor power.
5. Quality assurance programme
A set of procedures was developed and is routinely performed to ensure proper functioning
of all systems and to maintain accurate calibration of beam monitor output in terms of the
absorbed dose delivered under reference clinical conditions. These procedures parallel those
used in conventional radiotherapy and were designed to fulfil technical specifications (TS)
for the FCB as well as the quality assurance programme for the conduct of human therapy
approved by the US Nuclear Regulatory Commission. The procedures summarized in table 1
are separated into three different categories; functional checks, output or constancy checks, and

8. 3732 K J Riley et al
beam characterizations or instrument calibrations. Compliance is documented by archiving
completed forms and a master schedule that tracks each procedure and indicates the next
necessary completion date.
Integral functional checks of all safety-related interlocks are performed on a monthly basis.
Proper functioning of equipment (e.g. temperature and flow monitors, nuclear instrumentation,
etc) is verified prior to each use of the facility through a system start-up checklist. Prior to
commencing clinical irradiations, an additional checklist is completed to ensure that patient-
related equipment such as cameras, intercoms and door controls are operational.
Output or constancy checks of the neutron beam, area radiation monitors, boron analysis
system and other detectors are generally completed as needed prior to either their use or a
clinical irradiation. The discriminator and voltage plateau checks for each beam monitor are
performed every six months.
Each beam configuration (e.g. beam aperture) must be characterized within six months
prior to its clinical use. A beam characterization consists of measurements along the central
axis of an ellipsoidal, water filled phantom to determine the absorbed dose under reference
clinical conditions. The results from these measurements are correlated with output from the
beam monitors and the treatment planning system so that irradiations can be administered
using a set of monitor units that are separately prescribed for each of the four beam monitors.
Instrumentation used during the characterization must also be calibrated. Ionization chambers
are calibrated against a national standard in terms of air kerma for 60Co at an accredited
dosimetry calibration laboratory every two years and constancy checks are performed on an
in-house photon source prior to each use. The boron analysis systems as well as the area
radiation monitors inside and outside the medical therapy room are also calibrated at regular
intervals.
6. Beam data
The technique of mixed-field dosimetry described previously for epithermal neutron beams
(Rogus et al 1994, Riley et al 2003) is applied to measure the neutron and photon absorbed
dose rates inside a 0.6 × 0.6 × 0.6 m3 water phantom with 10 mm thick PMMA walls. The
dimensions of the phantom are much greater than the 160 mm diameter of the largest aperture
to minimize the effects of leakage radiation for measurements near the edge of the field. The
phantom was positioned with the front face against the end of the patient collimator without
an air gap. Depth dose profiles were measured along the central axis and at a horizontal
displacement of 80 mm from the central axis of the beam. Horizontal cross-field profiles
(displacement ranging from −100 to 100 mm) were obtained at a depth of 25 mm near the
total dose maximum. These data complement the characterization measurements routinely
performed as part of the quality assurance program and serve to benchmark the source term
used for treatment planning calculations. These data are also being used for the international
programme combining clinical results from BNCT centres worldwide (Harling et al 2002b).
The measured photon absorbed dose rate has an estimated uncertainty (1σ ) of 4.4%, while
that attributed to thermal neutrons ranges from 4.6% near the surface of the phantom to 6.5%
at depth due to differences in counting statistics of the activation foils. Fast neutrons account
for only approximately 5% of the total measured response of the A-150 walled ionization
chamber and consequently the large correction necessary in the twin chamber method limits
the accuracy of determination. Fast neutron absorbed dose rates near the surface have an
estimated uncertainty of 61%, while those at depths of 50 mm and greater are 125%.
The depth dose profiles measured on the central axis of the phantom and at a lateral
displacement of 80 mm near the edge of the field are shown in figures 5(a) and (b), respectively,

9. A state-of-the-art epithermal neutron irradiation facility for neutron capture therapy 3733
(a)
(b)
(c)
◦
Figure 5. Absorbed dose rates for photons ( ), thermal neutrons ( ) and fast neutrons
(♦) measured in a 0.6 × 0.6 × 0.6 m3 water phantom for the 160 mm diameter field and scaled
to a converter operating power of 83 kW with depth-dose profiles (a) on the central axis of the
beam (b) displaced 80 mm from the central axis and (c) cross-plane profiles measured at a depth of
25 mm with the aperture indicated by dashed lines.

10. 3734 K J Riley et al
scaled to a converter operating power of 83 kW. The shallowest measurements on the depth
dose curve are near the expected dose maximum for the photon and thermal neutron dose
components, which exhibit a steady decrease with depth in phantom. The measured fast
neutron absorbed dose rates are comparatively small, particularly at depth in phantom and for
the off-axis profile. Figure 5(c) shows cross-plane profiles of the different dose components
measured at 25 mm depth in the phantom. All of the dose components decrease steadily
with increasing displacement and appear symmetric about the central axis of the beam. The
80–20% penumbrae for the different dose components are large (>40 mm) compared to
other modalities where the spatial profile of the beam must be carefully tailored to match the
boundaries of the planning target volume. In BNCT, a uniform distribution of thermal neutrons
within the target volume is desirable because without significant levels of beam contamination,
as exhibited by the FCB, the dose will be principally confined to tumour regions where the
boron concentration is expected to be highest.
7. Summary
The fission converter concept has proven suitable for obtaining a high purity beam of epithermal
neutrons for BNCT with intensities that result in irradiation times as short as a few minutes.
The relatively low power (83 kW) generated in the converter illustrates the efficiency of the
fission process for producing epithermal beams and the feasibility of small reactor-based
sources for dedicated use in a hospital.
Though the MITR-II is not dedicated solely for BNCT research, the FCB and PGNAA are
independent of other experiments and do not affect regular reactor operation. Several nearby
New England hospitals can conveniently conduct outpatient irradiations at MIT, drawing from
a large local population. The beam line is presently optimized for brain tumour studies although
it can be easily reconfigured to treat other disease sites. The operational characteristics of the
facility closely match those established for conventional radiotherapy, which together with a
near optimum beam performance ensure that the FCB is capable of determining whether the
radiobiological promise of this cellular tumour targeting therapy can be realized in routine
practice.
Acknowledgment
This work has been supported by the US Department of Energy under contract number
DEFG02-96ER62193.
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