MRI guided proton therapy

Participants:
B.W. Raaymakers, J.J.W. Lagendijk, M. van Vulpen, Joris Hartman

Proton radiation therapy versus photon radiation therapy

An advantage of using protons for radiation therapy is the so called Bragg peak: protons experience an energy dependent absorption in tissue which makes the energy deposition sharply peak in depth (the Bragg peak) and no energy is deposited behind this peak (figure 1). The radiation beam literally stops at the Bragg peak. Larger fields can be created by adding Bragg peaks. As a result, for most clinical applications, it is expected that the integral dose to the patient will be lower with protons than when using photons.  This feature makes protons in potential better suitable for irradiation of childhood cancer.



Figure 1: Comparison of depth profiles from proton therapy and photon therapy. The left hand panel shows in blue the Bragg peak of multiple proton beams from 1 direction. Together these define the spread out Bragg peak (SOBP) region (grey area) that span the tumour volume. In red the depth dose curve for a single photon beam from 1 direction, if one covers the same tumour volume with a single photon beam, the red area is the excess dose (Image taken from wikipedia). The right hand panel is a modification of the left hand panel. Radiotherapy is never performed with a single beam, opposing beams or cross fire beams are being used. In the right panel two opposing photon beams are used to cover the tumour volume. The excess dose has now decreased, the exact decrease depends on the size of the tumour volume as the SOBP will have increasingly higher entrance levels with increasing tumour volume, but the fact that the proton beam stops in tissue is still an intrinsic advantage of proton therapy for limiting the integral dose.

Conventional photon radiotherapy has been improved over the last decades to also minimise the dose to the surroundings and maximizing the dose to the target by applying intensity modulation radiotherapy (IMRT). Also proton therapy benefits from using multiple beams and intensity modulation (IMPT). The advantage on target coverage of either IMRT and IMPT is still under debate, but less integral dose in favour of IMPT is expected in case equal margins are being used.


High precision MRI guided proton therapy

In principle the Bragg peak can also be exploited to apply an unrivalled sharp dose gradient between the target and an organ at risk, but for this application the exact depth in tissue of the tumour must be known. With present image guidance this is only the case for some tumours in the brain and head and neck, tumours in the body have uncertain positions due to differences in organ filling and also move with breathing.

At the UMC Utrecht we are investigating of the Bragg peak can be used for high precision stereotactic irradiation for moving targets. This relies, even more than for photon therapy, on image guidance: both inter- and intra-fraction motion can severely deteriorate a proton therapy dose distribution. While mis-positioning of a target volume by a few mm will result in a few % dose change for photon therapy, it can lead to a 100% dose change for proton therapy as is clear from figure 1. One approach is to make the proton therapy dose distribution less sensitive, robust, for such anatomical motion but doing so will not exploit the benefit of the Bragg peak. The Bragg peak lowers the integral dose but thus also provides a severe complication. While with photon irradiation we only have to aim in the right direction, with a small well defined beam, with proton therapy, we do have to direct the beam but also have to predict where the beam will stop. This so-called range uncertainty is that strong that additional margins are required which can kill the benefits of proton therapy especially in non-stationary and moving targets. So we aim to overcome the impact of anatomical motion by real-time image guidance, more specifically by MRI guided proton therapy.


Integral dose and the impact of margins

Most comparative studies between photon and proton irradiation imply that the positioning of the beams according to the anatomy is of equal quality, which is typically not the case. Huge improvements are being made with conebeam CT guided photon radiotherapy. New developments like real-time and online MRI guidance (MRI linac) promise unequalled targeting quality, making enormous margin reductions possible. The impact of margins are substantial as illustrated by Verellen et al. (2007) using an orange, see figure 2, the shell typically has the same volume as the orange itself. Such volume reductions easily outperform the benefit in integral dose reduction due to the Bragg peak.

If proton therapy does not have appropriate image guidance to account for instance for intra-fractional, breathing related motion, large margins are required. At this moment having MRI guidance for protons is a research line with a commercial product at least 10 years away. This implies that the present proton systems require wide margins with a larger high dose volume and thus unnecessary high dose to normal tissues but also a larger integral dose. The present development of MRI guided external beam IMRT (Elekta and Philips) has the potential to easily outperform the present proton techniques for all high precision locations. This seriously urges for research into MRI guided proton therapy and put great stress on the success of conventional proton initiatives. The big advantage of reducing the integral dose by proton therapy can thus only persist when appropriate image guidance is performed.

Figure 2: Orange and its peel representing a target volume and its margin. A 6.5 mm thick margin (peel) consists of the same volume as a 5 cm diameter target (orange), taken from Verellen et al. 2007.

Assessing anatomical motion and range variation by MRI

Image guided proton therapy faces two challenges: target localization and proton beam range verification. The target localization is a similar challenge as with the MRI accelerator. We are working on geometrically correct MRI, fast enough to capture 3D anatomical motion. This can be done by fast 3D MRI but also by updating a 3D anatomy model by using 1D or 2D MRI, possibly in combination with shape models or prediction modelling (See section MRI linac).

We are investigating the use of dedicated MRI sequences to establish the radiological path length in order to guide the Bragg peak to exactly the right depth (see 4D MRI section).


Hybrid MRI proton therapy system

A hybrid MRI proton therapy system is not available at this moment. The plan is to first mature the hybrid MRI radiotherapy accelerator for photon therapy to establish clinical experience with on-line MRI guidance. In parallel different concepts for a hybrid MRI proton system will be evaluated. One approach could be using one or two fixed proton beams and move the patient, under MRI guidance with respect to the beam. There are many technical hurdles to be taken to realize such machine. As briefly discussed in Raaymakers et al. (2008), the issues are similar to the hybrid MRI photon radiotherapy system: the magnetic interference, the radiation delivery from outside of the MRI and the magnetic field induced dose effects (this is discussed below in more detail). Additionally, with proton beams the depth has to be measured in real time, requiring fast MRI and tissue characterization. Still the solutions are not always similar, for instance, conventionally the proton accelerator head is close to the patient to minimise radiation losses and proton straggling in air. For modern proton therapy devices with pencil beam scanning this means the beam steering equipment is close to the MRI with potential interference as a consequence.

Figure 4: Possible configuration of a hybrid MRI proton system, taken from patent application 20110230754 by Johan Overweg, Philips Hamburg, Germany.

Impact of a transverse magnetic field on the proton therapy dose distribution

In photon therapy there is an impact of a transverse magnetic field on the dose distribution. Especially at tissue-air interfaces, electrons, released by the photon irradiation, will return back to the tissue due to the Lorenz force instead of scattering away. The Electron Return Effect (ERE) yields a dose increase up to 30-40% of the local dose depending on a.o. the surface orientation. This effect can be compensated by using cross fire beam arrangements as is done in our MRI linac concept.

For proton therapy, the impact of a transverse magnetic field from ERE is negligible. This is due to the fact that the electrons released by the proton irradiation have a very low energy, making the electron path lengths very short and so the total number of electrons scattering away from a tissue air interface is far less than for photon therapy. In fact, so much less that the ERE can be neglected in dose calculations (See Raaymakers et al., 2008 or the link to the 2008 AAPM poster presentation on this topic from the link below).

For proton therapy there is another impact on the radiation beam, namely, the proton beam itself is deflected by the magnetic field (see above poster). This is a deterministic impact and can even be calculated analytically as shown by Wolf and Bortfeld (2012).


For a full PDF of the poster see the link below

At this moment we are preparing a project of MRI guided protons. A first step is the construction of a treatment planning environment in which the treatment planning studies can be performed. We are proud that at the 2015 ESTRO forum the paper of Joris Hartman with as title: ‘Dosimetric feasibility of intensity modulated proton therapy in a transverse magnetic field of 1.5 Tesla’, is in the highlight section.

 

References