12th Int. Beam Instrum. Conf.
ISBN: 9 7 8 - 3 - 9 5 4 5 0 - 2 3 6 - 3IBIC2023, Saskatoon, CanadaJACoW Publishing
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MiniBEE - MINIBEAM BEAMLINE FOR PRECLINICAL EXPERIMENTS*J. Reindl†, A. Rousseti, J. Neubauer, G. Datzmann1, G. Dollinger
Universität der Bundeswehr München, Neubiberg, Germany
G. Kourkafas, J. Bundesmann, A. Dittwald, A. Denker2, Helmholtzzentrum Berlin, Berlin, Germany
1
also at Datzmann Interact & Innovate GmbH, Munich, Germany
2
also at Berliner Hochschule für Technik, Berlin, Germany
Abstract
Spatial fractionated radiotherapy using protons, socalled proton minibeam radiotherapy (pMBT) was developed for better sparing of normal tissue in the entrance
channel of radiation. Progressing towards clinical use,
pMBT should overcome current technical and biomedicallimitations. This work discusses a preclinical pMBT facility, currently built at the 68.5 MeV cyclotron at the Helmholtz Zentrum Berlin. The goal is to irradiate small animals
using focused pMBT with a sigma of 50 µm, a high peakto-valley dose ratio at center-to-center distance as small as
1 mm and beam current of 1 nA. A first degrader defines
the maximum energy of the beam. Dipole magnets andquadrupole triplets transport the beam to the treatment
room while multiple slits properly form the transverse
beam profiles. A high magnetic field gradient triplet lens
forms the minibeams in front of the target station and, scanning magnets are used for a raster scan at the target. An
additional degrader, positioned close before the focusing
spot and the target, further reduces the energy, forming a
spread-out Bragg peak. A small animal radiation researchplatform will be used for imaging and positioning of thetarget.

INTRODUCTION
Radiation therapy (RT) aims to maximize the delivered
dose in the tumor while minimizing the dose to the normaltissues [1]. Proton beams can contribute to that goal due totheir advantageous physical properties [2]. They deposit
low dose at the entrance and the maximum dose is deposited in a well-defined range, based on their initial energy.
Additional methods of protecting the healthy tissues are thetemporal and spatial fractionation. The concept of Spatially
Fractionated Radiation Therapy (SFRT) is the fragmentation of dose in space creating at the entrance a periodical
pattern of regions with high (peak) and low (valley)doses [3]. Proton minibeam radiation therapy (pMBT) is aninnovative treatment method which exploits the advantages of proton beams and spatial fractionation [4, 5].
Minibeams have a transverse beam size (σ) in the submillimeter range and they are delivered with an interdistance,
which is called center-to-center (ctc) distance, in the millimeter range in order to cover the tumor laterally. In thisway, the created alternated pattern of peaks and valleys in
the entrance spares the healthy tissues. When proton beams
transverse the matter they broaden due to multiple____________________________________________* Work supported by German Ministry of Defence BMVg
† Judith.reindl@unibw.deCoulomb scattering (MCS) ending up to cover the tumor
homogeneously (see Fig. 1).

Figure 1: Simulated dose distribution of pMBT applying
68 MeV proton minibeams (𝜎 =98 μm and ctc = 1.4 mm)
in a water phantom assuming a tumor in 2.9 - 3.9 cm depth.
The spread-out Bragg peak (SOBP) was obtained by positing a range shifter close to the phantom.
The in-vivo studies conducted so far have highlighted
the superiority of pMBT over conventional RT. One of thefirst proof-of-principle experiments, in which the right earof the mice were irradiated with a broad proton beam orwith an array of 16 minibeams (σ=180 μm and with
ctc=1.8 mm), showed that the acute side effects can be bypassed [6]. Another important in-vivo experiment investigated the dependence of side effects to the σ of thebeam [7]. Also in this case, the right ear of the mice wereirradiated with an array pattern of proton minibeams withdifferent σ and the same ctc. The results showed that better
sparing can be achieved with smaller beam sizes. Furthermore, a study in which rats with RG2 glioma were irradiated with pMBT or conventional RT schemes showed thatrats irradiated with minibeams had better survival rate andless side effects [8]. All the aforementioned results gave aprominence to pMBT over conventional RT due to the better sparing of healthy tissue. However, the biologicalmechanisms underlying that phenomenon are not clear yet.
A preclinical pMBT facility can contribute to intense andsystematic research and tissue sparing effects have to bedemonstrated on various tissues and beam settings in orderto fully investigate the aspects and prospects of pMBT. In
this paper we describe the concept of a preclinical proton
minibeam radiotherapy facility for small animal irradiation
at the Helmoholtz-Zentrum in Berlin (HZB) [9].

BEAMLINE DESIGN
The proposed beamline concept should fulfill some constraints related to the beam energy, the beam energy degra-MOP002
3401 Overview and Commissioning

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Figure 2: Layout of the pMBT beamline design at HZB. The beam goes from the left downwards to the right and upwards.
Quadrupoles are shown in red, dipoles in blue and steerers in green.
dation and the beam dimensions in the target in order to besuitable for preclinical experiments in animals. The proposed beamline design is demonstrated in Fig. 2. The cyclotron at HZB generates a 68 MeV proton beam which has
a maximum penetration depth ∼ 4 cm (in water), appropriate for small animal experiments. The energy can be degraded by a ”Hybrid range shifter system” in a twostep process. Firstly, the beam energy, as extracted from the cyclotron will be reduced by a degrader, defining the maximum
penetration depth. Then, a range shifter placed a closed tothe target will further degrade the energy, creating a SOBP
to fully cover the tumor. After the first energy degrading,the beam can be transported towards the target room by using a set of two 90° dipole magnets and four quadrupole
triplets (QUAK1, QUAK3, QUAK4, QUAK5). Downstream of the second dipole magnet a focusing system issituated consisting by one quadrupole triplet (QUATC1),
with high magnetic field gradient, and two drift lengths(𝑥1, 𝑥2). The drift length 𝑥1 is the distance between thefocus plane of the second 90° dipole magnet and theQUATC1 and 𝑥2 is the distance between the QUATC1 andthe isocenter. In order to achieve the demagnification of thebeam’s size, the drift length 𝑥1 is almost five times larger
compared to 𝑥2 (𝑥1 ≈ 5 𝑥2). Upstream of the QUATC1,
two sets of scanning magnets are placed aiming to haveraster-scanning application of the minibeams in the target.
In the last part of the beamline, the beam is extracted by
the exiting window, which consists of the vacuum tube anda Kapton foil. Right after there is a dosimetry unit and thenthe beam transverse a few cm of air and its energy is further
degraded, when it is necessary, until the target. For the accurate positioning and imaging of the animal, a small animal radiation research platform (SARRP, Xstrahl GmbH,Ratingen, Germany) will be used. The suggested beamline
aims to generate proton pencil minibeams with a transversal size of σ=50 μm, ctc ∼ 1 mm, for raster-scanning application and beam current ∼ 1 nA.

BEAMLINE SIMULATIONIn this work, we performed preliminary beamline simulations for the presented minibeam beamline concept (seeabove). All the simulations have been done using
Trace 3-D [10], which is a first-order beam dynamic code.
The starting point of the simulations, named "SLJ1", is after the beam extraction from the cyclotron (see Fig. 2). Thebeam parameters at SLJ1 are know from measurementsthat have been already conducted in HZB. The measurements have been performed at a current of 22 nA, but morethan 100 nA are easily available with the same beam parameters. The beam is transported from SLJ1 until the isocenter, which is located in the SARRP, using only the 90°
dipole magnets and the quadrupole triplets, as it is illustrated in Fig. 3. In Table 1 the transversal beam parameters(beam size: σ and beam divergence: σ′) are presented forMOP002
01 Overview and Commissioning

35

Content from this work may be used under the terms of the CC-BY-4.0 licence (© 2023). Any distribution of this work must maintain attribution to the author(s), title of the work, publisher, and DOI

12th Int. Beam Instrum. Conf.
ISBN: 9 7 8 - 3 - 9 5 4 5 0 - 2 3 6 - 3

Content from this work may be used under the terms of the CC-BY-4.0 licence (© 2023). Any distribution of this work must maintain attribution to the author(s), title of the work, publisher, and DOI12th Int. Beam Instrum. Conf.
ISBN: 9 7 8 - 3 - 9 5 4 5 0 - 2 3 6 - 3

IBIC2023, Saskatoon, Canada
JACoW Publishing
ISSN: 2 6 7 3 - 5 3 5 0d o i : 1 0 . 1 8 4 2 9 / J A C o W - I B I C 2 0 2 3 - M O P 0 0 2Figure 3: Beamline simulations in Trace 3-D: The simulations include only the magnetic elements (dipole magnets andtriplets) starting after the beam extraction from the cyclotron (SLJ1) until the isocenter (SARRP).
both SLJ1 and the isocenter. These preliminary results
demonstrate that the suggested setup can achieve a beam
size demagnification of ∼ 1/4 in the isocenter in both axes.
Table 1: Beam Parameters at SLJ1 and at the Isocenter
𝜎𝜎𝜎𝜎

SLJ1
800 µm
480 µm3.67 mrad1.19 mrad

Isocenter
220 µm118 µm
9.83 mrad
4.84 mrad

CONCLUSION
The presented beamline concept can properly reduce thebeam size in the isocenter by a factor of ∼4. In the next
steps, the slits should be positioned to properly shape thetransversal phase spaces to meet the desired beam parameters. In addition, it is crucial to study the effects of the degrader in the beam current and the beam size. For all thesepurposes, programs which also include Monte Carlo simulations are going to be used to properly simulate the beamtransport and its interaction with materials. The results willcontribute to a fully comprehensive investigation of thebeamline and finally, to the construction of the MiniBEEfacility.

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MOP0023601 Overview and Commissioning