WO2016099264A1

WO2016099264A1 - Imaging method and system for verification of a treatment plan in hadron therapy

Info

Publication number: WO2016099264A1
Application number: PCT/NL2015/050870
Authority: WO
Inventors: Oksana Olegivna KAVATSYUK; Marc-Jan VAN GOETHEM; Sijtze BRANDENBURG
Original assignee: Rijksuniversiteit Groningen; Academisch Ziekenhuis Groningen; Stichting Voor De Technische Wetenschappen
Priority date: 2014-12-18
Filing date: 2015-12-17
Publication date: 2016-06-23
Also published as: NL2014012B1

Abstract

An imaging method and system for verification of a treatment plan (A). A phantom volume (V) is provided consisting of a material (10m) having dose absorbing properties similar to a biological tissue according to the treatment plan (A). Dose parameters (Q) of a hadron beam (B) are set according to the treatment plan (A). The hadron beam (B) is directed into the phantom volume (V) according to the dose parameters (Q). Light (L) emitted from the phantom volume (V) is measured. A dose distribution (D) of the hadron beam (B) in the phantom volume (V) is calculated based on the measured light (L). The light (L) is measured by imaging a lateral side (14,15) of the phantom volume (V) while the material (10m) of the phantom volume (V) comprises at least 90 mass percent water.

Description

IMAGING METHOD AND SYSTEM FOR VERIFICATION OF A TREATMENT PLAN IN HADRON THERAPY

TECHNICAL FIELD AND BACKGROUND

The present invention relates to an imaging method and system for verification of a treatment plan, in particular for quality assurance of dose delivery in hadron therapy.

Dose delivery in radiotherapy with hadrons (e.g. protons or other ions) is an emerging treatment modality in radiation oncology that reduces the radiation dose in, and the volume of, inevitably co-irradiated healthy tissue in the vicinity of a tumor. It has the potential to significantly improve the treatment outcome for specific indications, in particular by reducing long term radiation induced side effects in healthy tissue. Dose delivery in hadron therapy is a complex process in which the intended three

dimensional dose distribution is "painted" with a very large number of pencil beams (e.g. up to 10⁴ beams). Furthermore, each pencil beam is characterized by parameters such as particle energy, beam direction, impact position, and fluence (number of particles). Therefore, a detailed quality assurance procedure to verify the proper execution of a treatment plan prior to the start of the treatment course is important to realize the high accuracy dose delivery required to achieve the clinical benefits.

The current clinical standard for verification of dose distributions is the use of a two-dimensional array of ionization chambers that is positioned at various depths in a water volume to which the dose is delivered prior to the treatment course. The water acts as a phantom volume having similar dose absorbing properties as the biological tissue to be irradiated. However, the conventional technique measures the delivered dose on a relatively coarse grid (typically 1 cm) and is slow because subsequent measurements have to be taken at up to 20 depths.

Furthermore, the technique is not suitable for dose delivery using pencil beam scanning, because the response of the ionization chambers is not independent of beam size and position with respect to the ionization chamber.

Archambault et al. (Med. Phys. 39 (2012) 1239) describe optical imaging of light produced during dose delivery to an organic scintillator using pencil-beam scanning with protons. However the scintillator materials are typically expensive and toxic. Furthermore, the scintillator material tends to deteriorate by radiation damage and therefore has to be replaced on a regular base. Finally, due to quenching, the detected signals need heavy calibration to calculate the expected dose delivery in a biological tissue.

Glaser et al. (Physics in Medicine and Biology 2014, 59) describe a simulation study for optical dosimetry of radiotherapy beams using Cherenkov radiation in water tanks. From the study it is concluded that for proton dosimetry, there exists a fundamental lack of Cherenkov emission at the Bragg peak, making the technique of little use. The article suggests that post-irradiation detection of light emission from radioisotopes could be useful. However, the non-localized effects of induced radionuclides provide weak correlation with the actual position of the deposited dose and are therefore not useful for accurate verification of a treatment plan as used herein. See also Helo et al. (Phys. Med. Biol. 59 (2014) 7107-7123)

Jang et al. (Optics Express Vol. 20, No. 13 (2012), 13907) describe a fiber-optic Cerenkov radiation sensor for proton therapy dosimetry. The sensor comprises a plastic (PMMA) optical fiber suspended in a water phantom in the irradiation field of the proton beam. The article describes measurements of Cerenkov radiation generated in the plastic optical fiber as a solution to measure Bragg peaks of therapeutic proton beams without the quenching effect of the organic scintillator. According to the article, in the case of therapeutic proton beams, whose commercial energies are below 235 MeV, Cerenkov radiation in the optical fiber is not induced directly by incident proton beams but induced by subsequent electrons, because the Cerenkov threshold energy of the proton beam is about 328 MeV for the PMMA. However, since the technique relies on the Cerenkov radiation generated in the fibre, getting a full image of the dose distribution may require scanning the sensor fibre, which is time consuming. Furthermore, the Cherenkov radiation by secondary electrons is highly directional (anisotropic) which may skew the measurement.

International application WO 2014/102929 Al describes a dose distribution measurement device that includes at least two cameras arranged on a plane perpendicular to the center axis of irradiation of a so called 'water phantom' mimicking a human body. The wall of the water phantom is formed of a transparent material such as an acrylic resin that transmits light and the water phantom is filled with a fluorescent substance containing liquid. The fluorescent substance containing liquid is generally referred to as a liquid scintillator that emits light on absorbing the particle beam. It is noted that the light emission may be nonlinear to an irradiation dose which typically result from quenching if the amount of fluorescent substance is relatively high. No further details of the liquid scintillator are described.

Accordingly, there remains a desire for further improvements in the verification of treatment plans for hadron therapy. In particular, there is a desire for a novel technique to measure the full three-dimensional dose distribution that is accurate and fast, easy to implement, inexpensive, and without the use of known (toxic) scintillators. SUMMARY

A first aspect of the present invention provides an imaging method for verification of a treatment plan according to claim 1. The imaging method comprises providing a phantom volume consisting of a material having dose absorbing properties similar to a biological tissue according to the treatment plan; setting dose parameters of a hadron beam according to the treatment plan; directing the hadron beam according to the dose parameters into the phantom volume; measuring light emitted from the phantom volume; and calculating a dose distribution of the hadron beam in the phantom volume based on the measured light from the phantom volume. The light is measured by imaging a lateral side of the phantom volume (i.e. a side of the phantom volume having a surface normal that is transverse to a propagation direction of the hadron beam) while the material of the phantom volume comprises at least 98 mass percent water.

A second aspect of the present invention provides a system for verification of a treatment plan according to claim 14. The system comprises a container for holding a phantom volume consisting of a material having dose absorbing properties similar to a biological tissue according to the treatment plan; a beam controller configured to control a hadron beam source and programmed for setting dose parameters of a hadron beam according to the treatment plan; and directing the hadron beam according to the dose parameters into the phantom volume; a light sensor for measuring light emitted from the phantom volume; and a dose analyser configured to receive measurements from the light sensor and programmed for

calculating a dose distribution of the hadron beam in the phantom volume based on the measured light from the phantom volume. The light sensor is configured to image a lateral side of the phantom volume while the material of the phantom volume comprises at least 98 mass percent water.

The invention is based on a surprising discovery that the dose deposition of a therapeutic hadron beam in pure water correlates with faint light emissions from the water itself, which light can be directly measured without the need for any further scintillator material. It is further

discovered that these light emissions are sufficiently isotropic and propagate sufficiently through the water volume to allow imaging of the light from a lateral side of the phantom volume. Accordingly, a side view projection of the light emissions can be recorded to facilitate providing a map of the dose distribution. Because the light emissions spatially correlate with the actual dose deposition the map can be very accurate. Furthermore, the accuracy is improved because there only minimal or no calibration needed, since water is already highly equivalent with biological tissue. Because the distribution of the dose related light emission can be detected from a lateral side, without the need for measuring at different depths, the technique can be very fast. The method can be easily implemented e.g. by projecting the captured light on a pixel based camera. The technique does not require expensive equipment (e.g. scanning fibres) or toxic materials. Accordingly, the technique is accurate and fast, easy to implement, inexpensive, and without the use of toxic scintillators

Without being bound by theory, it will be noted that the currently discovered light emissions are not based on Cerenkov radiation because the energy (momentum) of the therapeutic proton beam (<235 MeV) is well below the Cerenkov threshold for protons in water. Also, the presently measured light signals are found to be isotropic, unlike Cerenkov radiation which is emitted in a specific cone with respect to the direction of the propagating beam. Furthermore, the measured light emissions cannot be modelled based on induced radionuclides because the hght emissions are found to spatially correlate with the actual dose distribution and because the light emissions are temporally correlated with the moment of deposition, unlike long living radionuclides whose decay would be detected via

secondary particles away from the dose position. Accordingly, the measured hght may be resulting from atomic and molecular excitation of the water by the hadron beam. The excitation may include a variety of effects such as ionization, radical formation, and radiation chemistry. It is noted that such atomic and molecular interactions are not part of the conventional models for high energy simulation studies. Accordingly, the presently discovered light emissions can not be found by such simulation studies but only by actual experiment, as the inventors have done. By placing a sensor having a surface normal that is transverse to the beam direction it may capture a side-view projection of the dose deposition with information at multiple depths in a single image. In other words, preferably the optical axis of the sensor is transverse (e.g.

substantially perpendicular) to the beam direction By measuring the light with a sensor outside the phantom volume, the sensor is not affected by the water or other chemicals in the volume. For example, a pixel based camera with a pixel array facing a lateral side of the phantom volume may be configured to record a lateral image of the light emitted as a result of the dose distribution.

By combining multiple lateral and/or longitudinal projections from different angles, a three dimensional map of the dose distribution can be reconstructed. For example, two lateral images of the light may be recorded via two transversely oriented surfaces of the lateral surfaces. For example, two perpendicular projections of the light produced by the dose distribution may be recorded simultaneously. Also more than two images may be captured and/or at different angles with respect to each other.

Lateral images may be recorded by positioning a camera with a sensor facing a lateral side of the phantom volume. Alternatively, or in addition, the projection of the lateral and/or longitudinal side of the phantom volume may redirected, e.g. via a mirror system in a light path between a lateral surface and the light sensor. The mirrors used can be flat or curved, e.g. parabolic. By covering the surfaces not used for recording the images, e.g. by a material that is non-reflecting and/or absorbing the measured light, interference of outside light through these non-used surfaces may be reduced. Alternatively, or in addition, by using a non-reflecting material on the unused sides of the phantom volume, interference from unwanted reflections can be prevented. A side of the phantom volume may be considered non-reflecting e.g. having a reflection coefficient of less than 0.02 (or two percent) for the light to be measured e.g. at normal incidence, preferably less than 0.01 (or one percent).

Delivery of a total dose to the volume may comprise the combined deposition of doses by a plurality of beams. Accordingly, directing the hadron beam into the phantom volume may comprise so called pencil-beam scanning wherein a plurality of hadron beams are directed into the phantom volume to deliver a total dose distribution. The dose deposition by the individual beams may be recorded separately or integral. For example, an image of the light of the dose distribution is recorded in an integral mode wherein a sum total of the light caused by the plurality of hadron beams is integrated. Alternatively, or in addition, measuring of the light is

synchronized with individual delivery of each of a plurality of hadron beams for recording separate images of a plurality of dose distributions

corresponding to the plurality of hadron beams. Alternatively, or in addition, an image for a group of pencil beams is recorded, e.g. a plurality of pencil beams having a certain energy.

The procedure for verification of the treatment plan may comprise additional steps preceding or following the light measurement. For example, a calibration algorithm may be used to convert the calculated dose

distribution of the hadron beam in the phantom volume to an expected dose distribution of the hadron beam in the biological tissue or vice versa, e.g. the treatment plan of the patient is "mapped" /"translated" into a dose

distribution in the material of the phantom. For example, the procedure may further comprise calibrating the calculated dose distribution of the hadron beam in the phantom volume, e.g. using an ionization chamber. Advantageously, because the phantom volume as used herein may consist mostly of water, a standard calibration using an ionization chamber in a water volume may be performed using the same phantom volume without the need for switching the absorber material. For example, the ionization chamber may be placed in the phantom volume as part of the same device, e.g. in the back of the volume, and brought into a measurement position during a calibration. For example, when a measured or calculated dose deviates from and expected or intended dose distribution, the dose parameters may be adjusted and the procedure be iterated until a satisfactory correspondence is achieved. For example, the dose parameters may comprise one or more of a particle energy (typically up to 235 MeV), beam impact position (e.g. X,Y), beam direction (e.g. impact angle), beam fluence (approximate number of particles per pencil beam). For example, the particle type may be changed, e.g. protons, helium ions, carbon ions etc. The charged particle beam is typically provided by means of a cyclotron, synchrotron, linear accelerator, or combinations thereof . In principle, any accelerator system suitable for hadron therapy may be used. While the light emission from the water can be directly measured using a sufficiently sensitive (e.g. CCD) detector, the inventors find that the measurement can be facilitated by adding and/or dissolving a small amount of fluorescent material to the water. The fluorescent material may convert ultraviolet light, resulting from the dose deposition by the hadron beam in the water, into visible light. It will be appreciated that visible light may have less absorption in the water and/or can be more easily captured using a standard (visible light) camera. For example, the material of the phantom volume essentially consists of water, wherein the measured light emitted from the phantom volume is generated by interaction of the hadron beam with the water itself. Alternatively, the material of the phantom volume comprises between 0.01 and 2 mass percent of a fluorophore for converting ultraviolet light, resulting from dose deposition by the hadron beam in the water, into visible light

When used, preferably the amount of fluorophore is kept small to prevent quenching and to maintain equivalency of the phantom volume with biological tissue, with minimal calibration required. Accordingly, it is found preferable to keep the amount of fluorophore relatively low, e.g. between 0 and 2 mass percent, preferably between 0.01 and 1 mass percent, e.g.

between 0.1 and 0.5 mass percent of the mass of the phantom volume.

Preferably, the fluorophore at a certain concentration has little or no influence on the dose absorption properties of the water, e.g. wherein an added fluorophore of concentrations up to 10 grams/litre the difference in dose deposition of a typical 2 Gy dose fraction in the solution with respect to that in (pure) water is at most 2 percent, preferably less, e.g. at most 1 percent. The less influence the fluorophore has on the absorption properties of the water, the easier the effect of fluorophore may be corrected

(calibrated).

Preferably, the fluorophore strongly absorbs UV-light and re- emits visible light with a high efficiency. For example, the fluorophore has a quantum yield of more than 0.1 for converting ultraviolet light, resulting from dose deposition by the hadron beam in the water, into visible light. Preferably the quantum yield is even higher, e.g. at least 0.3, at least 0.4, or at least 0.5. The higher the quantum yield, the more visible light may be measured resulting in improved signal over noise.

Preferably the fluorophore is (relatively) non-toxic e.g. having a

Mouse LD50 (oral administration) of at least 100 mg/kg, preferably at least 500 mg/kg, more preferably at least 1000 mg/kg. A LD50 value indicates a lower toxicity of the chemical compound. In particular when dissolved in small concentrations, the mixture of water and fluorophore may be considered substantially non-toxic. Accordingly, handling and disposure of the mixture can be without complications.

Suitable fluorophores meeting one or more of the desired criteria may include substances comprising aromatic carbohydrates, in particular quinine [systematic (IUPAC) name: (R)-(6-Methoxyquinolin-4- yl)((2S,4S,8R)-8-vinylquinuclidin-2-yl)methanol]. Typically the fluorophore may be dissolved from a salt with a counter ion such as sulphate. For example quinine salts such quinine sulphate di- or monohydrate can be used. Of course also other counter ions can be used. Dissolved quinine strongly absorbs UV-light and re-emits visible light with a high efficiency having (e.g. typical quantum yield 0.58). Quinine is relatively non-toxic, e.g. having a mouse LD50 (oral administration) of 1160 mg/kg. It is noted that while the use of quinine as fluorescent for converting ultraviolet to visible light may be known as such, this is not in combination with hadron dosimetry in water phantom. It is now found that the light output for a 10 grams/litre solution of quinine sulphate in water is sufficient for accurate measurement of the typical 2 Gy dose fraction delivered to patients in hadron based radiation therapy. At this concentration the difference in dose deposition in the solution with respect to that in water is found to be at most 1% and can easily be corrected for. Quinine may be acting not only as a fluorophore but also as a scintillator. At lower concentrations, the relative contribution as fluorophore can be dominant, while at higher

concentrations, the contribution as scintillator may be dominant.

Comparison of the dose-depth curve obtained from the optical image with that measured with an ionisation chamber in the water tank shows a quenching at the high linear energy transfer (LET) at the end of the particle trajectory that is comparable with that observed for organic scintillators. For pure water and low (<0.1 gram/litre) quinine sulphate concentrations no significant quenching was observed. This suggests that two mechanisms play a role in the light production: fluorescence without quenching and scintillation with quenching. The spectral composition of the observed light was at all concentrations found to be consistent with the known emission spectrum of quinine sulphate. Additional experiments were performed to assess the radiation hardness, shelf life and sensitivity for dissolved oxygen. These experiments showed no radiation induced

degradation up to a dose of at least 1000 Gy, excellent reproducibility after three months storage and, in contrast to other organic scintillators, no sensitivity to dissolved oxygen. Also, no difference in response between normal tap water and high purity water was observed. For example, the high purity water may have less than 0.1 mass percent impurities or even less than 0.01 mass percent impurities.

The rest of the phantom volume, besides the fluorophore, may consist of (pure) water (H2O), e.g. wherein the phantom volume has a fraction of more than 90 mass percent water, 95 mass percent water, more than 98 mass percent water, more than 99 mass percent water, more than 99.5 mass percent water, more than 99.8 mass percent water, more than 99.9 mass percent water, or even 100 percent water. At higher

concentrations of water the equivalence to the standard for measuring dose absorption is better. Alternatively, or in addition, it can be allowable to have small quantities of other materials (e.g. naturally occurring or pollutants) dissolved in the water. For example, the inventors found no significant influence when using (Dutch) tap water compared to ultra pure water. To minimize the influence, preferably the amount of other dissolved materials is kept small, e.g. less than 1 mass percent, preferably less than 0.5 mass percent, e.g. between 0.001 and 0.1 mass percent of the phantom volume. BRIEF DESCRIPTION OF DRAWINGS

These and other features, aspects, and advantages of the apparatus, systems and methods of the present disclosure will become better understood from the following description, appended claims, and accompanying drawings wherein:

FIG 1 schematically shows an isometric view of an embodiment of an imaging method and system;

FIGs 2A and 2B schematically show top views of an embodiment of an imaging method and system;

FIG 3A and 3B show experimentally obtained plots; FIG 4A schematically illustrates a mechanism for converting UV light into visible light by means of a fluorophore;

FIG 4B schematically illustrates a mechanism for direct generation of visible light by dose deposition;

FIG 5A schematically illustrates atomic and molecular excitation resulting in isotropic light emission;

FIG 5B schematically illustrates the Cerenkov mechanism resulting in directional (anisotropic) light emission;

FIG 6 schematic illustrates a treatment facility.

DESCRIPTION OF EMBODIMENTS

Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly

understood by one of ordinary skill in the art to which this invention belongs as read in the context of the description and drawings. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein. In some instances, detailed descriptions of well-known devices and methods may be omitted so as not to obscure the description of the present systems and methods. Terminology used for describing particular embodiments is not intended to be limiting of the invention. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. The term "and/or" includes any and all combinations of one or more of the associated listed items. It will be understood that the terms "comprises" and/or "comprising" specify the presence of stated features but do not preclude the presence or addition of one or more other features. It will be further understood that when a particular step of a method is referred to as subsequent to another step, it can directly follow said other step or one or more intermediate steps may be carried out before carrying out the particular step, unless specified otherwise. Likewise it will be understood that when a connection between structures or components is described, this connection may be established directly or through intermediate structures or components unless specified otherwise. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control.

The invention is described more fully hereinafter with reference to the accompanying drawings, in which embodiments of the invention are shown. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. The description of the exemplary embodiments is intended to be read in connection with the accompanying drawings, which are to be considered part of the entire written description. In the drawings, the absolute and relative sizes of systems, components, layers, and regions may be exaggerated for clarity. Embodiments may be described with reference to schematic and/or cross-section illustrations of possibly idealized embodiments and intermediate structures of the invention. In the

description and drawings, like numbers refer to like elements throughout. Relative terms as well as derivatives thereof should be construed to refer to the orientation as then described or as shown in the drawing under discussion. These relative terms are for convenience of description and do not require that the system be constructed or operated in a particular orientation unless stated otherwise. FIG 1 schematically shows an isometric view of an embodiment of an imaging method and system 100 for verification of a treatment plan A.

The imaging method comprises providing a phantom volume V consisting of a material 10m having dose absorbing properties similar to a biological tissue according to the treatment plan A. The imaging method further comprises setting dose parameters Q of a hadron beam B according to the treatment plan A. The imaging method further comprises directing the hadron beam B according to the dose parameters Q into the phantom volume V. The imaging method further comprises measuring light L emitted from the phantom volume V. The imaging method further comprises calculating a dose distribution D of the hadron beam B in the phantom volume V based on the measured light L from the phantom volume V.

The system 100 comprises a container 10 for holding a phantom volume V consisting of a material 10m having dose absorbing properties similar to a biological tissue according to the treatment plan A. The system further comprises or is coupled to a beam controller (not shown). In one embodiment, the system and/or beam controller is configured to control a hadron beam source and programmed for setting and/or monitoring dose parameters Q of a hadron beam B according to the treatment plan A; and directing the hadron beam B according to the dose parameters Q into the phantom volume V. The system further comprises a light sensor 21,22 for measuring light L emitted from the phantom volume V. The system further comprises a dose analyser 30 configured to receive measurements from the light sensor 21,22 and programmed for calculating a dose distribution of the hadron beam B in the phantom volume V based on the measured light L from the phantom volume V.

In one embodiment, the light L is measured by imaging a lateral side 14, 15 of the phantom volume V transverse to a propagation direction Z of the hadron beam B. In one embodiment, the light sensor 21,22 is configured to image a lateral side 14, 15 of the phantom volume V transverse to a propagation direction Z of the hadron beam B. In one embodiment, the material 10m of the phantom volume V comprises at least 98 mass percent water. In one embodiment, the material 10m of the phantom volume V comprises between 0.01 and 2 mass percent of a dissolved fluorophore (see e.g. FIG 4).

In one embodiment, an interaction of the hadron beam B with material 10m of the phantom volume V causes a dose distribution D in the phantom volume V, wherein light L is emitted from the phantom volume V according to the dose distribution D. In one embodiment, a light sensor 21,22 is configured to receive light Lx,Ly from the phantom volume V in an emission direction X,Y lateral to a direction Z of the hadron beam B. In one embodiment, the light L is measured by a light sensor 21,22 outside the phantom volume V, wherein a lateral side 14, 15 of the phantom volume V is in a light path Lx,Ly between a deposited dose D of the hadron beam B and the light sensor 21,22. In one embodiment, the light sensor 21,22 comprises a pixel based camera with a pixel array facing a lateral side 14, 15 of the phantom volume V transverse to a direction Z of the hadron beam B, wherein the camera is configured to record a lateral image XZ, YZ of the light Lx, Ly emitted as a result of the dose distribution D.

In one embodiment, the material 10m of the phantom volume V is held by a container 10 comprising an entry surface 11 configured to receive the hadron beam B, a back surface 12 opposite the entry surface 11, and lateral surfaces 13, 14, 15, 16 connecting the entry surface 11 to the back surface 12. In one embodiment, at least one of the lateral surfaces 14, 15 is transparent to the measured light L for recording a lateral image ΧΖ,ΥΖ of the light Lx, Ly there through. In one embodiment, one or more of the surfaces 11, 12, 13, 16 not used for recording the lateral image XZ, YZ are non-reflective to the measured light L. In one embodiment, two

perpendicular projections of the light L produced by the dose distribution D are recorded. In one embodiment, two lateral images XZ, YZ of the light Lx, Ly are recorded via two transversely oriented surfaces 14, 15 of the container 10. In one embodiment, a lateral image YZ is recorded via a mirror 14M in a light path Lx between a lateral surface 14 and the light sensor 21.

In one embodiment, directing the hadron beam B into the phantom volume V comprises pencil-beam scanning. In one embodiment, a plurality of hadron beams is directed into the phantom volume V to deliver a total dose distribution D. In one embodiment, an image of the light L of the dose distribution D is recorded in an integral mode wherein a sum total of the light caused by the plurality of hadron beams is integrated. In one embodiment, measuring of the light L is synchronized with individual delivery of each of a plurality of hadron beams for recording separate images of a plurality of dose distributions D corresponding to the plurality of hadron beams. In other embodiments, multiple hadron beams can be imaged in a single measurement, e.g. keeping a camera shutter open while a plurality of pencil beams are directed into the phantom volume V.

One embodiment further comprises adjusting the dose parameters based on the calculated dose distribution and repeating the method for verification of a treatment plan A according to the adjusted dose

parameters. In one embodiment, the dose parameters Q of the treatment plan "A" comprise one or more of a particle type, (e.g. proton, helium ion, carbon ion), particle energy, beam impact position, beam direction, and/or fluence. In one embodiment, the hadron beam is a proton beam. In one embodiment, the hadron beam is generated by means of a particle accelerator (not shown).

FIGs 2A and 2B schematically show top views of an embodiment of an imaging method and system for verification of a treatment plan.

One embodiment comprises calibrating the calculated dose distribution of the hadron beam B in the phantom volume V. One

embodiment comprises providing an ionization chamber 40 (e.g. a two- dimensional array of ionization chambers) in the phantom volume V, and moving the ionization chamber 40 between a parked position P0 (FIG 2A) and a calibration position PI (FIG 2B). In the parked position P0 the ionization chamber 40 is outside a location where the dose distribution D is deposited, wherein the dose distribution D is measured by the light sensor 21,22. In the calibration position PI the ionization chambers 40 measures the dose distribution D. One embodiment comprises using a calibration algorithm (e.g. obtained by the ionization chamber 40) to convert the calculated dose distribution D of the hadron beam B in the phantom volume V to an expected dose distribution of the hadron beam B in the biological tissue.

In one embodiment, as shown in FIG 2A, the ionization chamber 40 is positioned at the backside 12 of the container 10 when it is in the parking position P0. In this way it will not be in the way of the beam B entering at the front side 11, or interfere with the measurement of the light L by the light sensor 21. In one embodiment, as shown in FIG 2B, the ionization chamber 40 is moved towards the front side 11 of the container 10 and placed at a position where the dose D is expected to be delivered. Of course, the ionization chamber 40 can also be parked at other positions than shown, e.g. inside or outside the phantom volume. It will be appreciated that the same material 10m can be used while measuring the light L (FIG 2A) by the sensor 21, and while calibrating the dose deposition by means of the ionization chamber 40 (FIG 2B). FIG 3A shows an experimentally obtained contour plot resulting from dose deposition by a 360 MeV ⁴He- beam in a quinine solution. The image is plotted as a function of position X and Y (millimeter) in the phantom volume captured by projecting a lateral image of the light resulting from the dose deposition onto CCD camera as described herein. The vertical dashed line indicates the front face of the phantom volume. FIG 3B shows experimentally obtained profile plots for dose deposition as a function of depth in the phantom volume. The plots are normalized to the peak of the Bragg curve for comparison. The plot indicated by the reference "IC" is measured by an ionization chamber. The other plot (W,q01,q03,ql0) are obtained by measuring the light of the dose deposition as described. Reference "W" indicates the result for dose deposition in water without added fluorescent. It will be appreciated that the plot shows an excellent correlation with the measurement obtained by the ionization chamber ("IC"), thus requiring little or no calibration.

References "qOl", "q03", and "qlO" indicate the results for dose deposition in water with added fluorescent in the concentration of 1 gram/litre, 3 gram/litre, and 10 gram/litre, respectively. It is noted that the added fluorescent enhances the signal to noise ratio while showing a good correspondence, at least in position of the Bragg peak, compared to the ionization chamber.

FIG 4A schematically shows a mechanism for converting UV light generated by the interaction of a hadron beam B with water, into visible light VIS by means of a fluorophore F. In one embodiment, the fluorophore F has a quantum yield of more than 0.1 for converting short-wavelength

(e.g. ultraviolet) light, resulting from dose deposition by the hadron beam B in the water, into longer wavelength (e,g, visible) light. In one embodiment, the dissolved fluorophore F comprises an aromatic carbohydrate. In one embodiment, the fluorophore F is relatively non-toxic with Mouse LD50 oral of at least 100 mg/kg. In one embodiment, as shown, the dissolved

fluorophore F comprises quinine.

FIG 4B schematically shows a mechanism for directly generating visible light VIS by means of a scintillator S interacting with the hadron beam B. Interestingly, it is presently found that quinine may act as a scintillator. The scintillator behaviour may occur at all concentrations, while being dominant particularly at higher concentrations. Accordingly, in one embodiment, the dissolved fluorophore additionally acts as a scintillator S that emits light as a result of dose absorption by the fluorophore F of the hadron beam B.

FIG 5A schematically shows atomic and molecular excitation of the water (H2O) by a hadron beam B. In the embodiment, the hadron beam B comprises a particle energy (momentum) below a threshold for generating Cerenkov radiation in the material of the phantom volume. In one

embodiment, at least 90 percent of the measured light L is resulting from atomic and molecular excitation of the water by the hadron beam B. In one embodiment, at least 90 percent, preferably at least 95 percent or higher, of the measured light L is isotropically emitted light originating from within 0.1 millimeter of the deposited dose D by the hadron beam B in the material of the phantom volume. This distinguishes the current interaction from other types of interaction, wherein dose is deposited in a first location, while light is emitted via secondary interactions from a second location distant from the first location. FIG 5B schematically shows generation of Cerenkov radiation by a hadron beam B having a particle energy above the Cerenkov threshold, for comparison. It will be noted that light L generated by the Cerenkov mechanism is highly directional. The threshold for generation of Cerenkov radiation depends on the phase velocity of light in the medium, which is inversely proportional to the refractive index ni of the medium. For water, the refractive index is approximately 1.33 wherein Cerenkov radiation is only expected for particles travehng faster than 0.75 times the speed of light (c). For protons having rest mass mo=938 MeV/c² the Cerenkov threshold momentum may thus be calculated to be about 1064 MeV/c. For heavier ions, the threshold is even higher. It will thus be noted that at clinical energies below 235 MeV, there is expected no Cerenkov radiation of the hadron beam in water.

For completeness, it is noted that the Cerenkov threshold as used herein corresponds to the threshold at which Cerenkov light is directly produced by the protons themselves, i.e. when the velocity of the protons is larger than 0.75c. On the other hand Cerenkov light can also be produced by secondary electrons resulting from the interaction of protons with matter, more in particular in water when the proton kinetic energy is larger than 226 MeV. For example, at 235 MeV kinetic energy there can be some

Cerenkov light from the secondary electrons which can be produced close to the proton track. In the present experiments care was taken to stay also below this hmit with the proton and ion energy. In any case, it is noted that along the path of protons of 235 MeV entering the water the Cerenkov light produced by secondary electrons will be limited to the first 2 - 3 cm; beyond that the energy of the proton has reduced too much. Finally, Cerenkov light may be emitted by positrons from the decay of short-lived radioactive nuclei, e.g. ¹⁵O and ⁿC. This Cerenkov light is also produced close to the track of the proton that produced the radioactive nucleus. FIG 6 shows a schematic perspective view of a treatment facility comprising a system 100 for verification of a treatment plan as described herein. In the shown embodiment, the system comprises three light sensors 21,22,23 configured to image not only the lateral sides of the container 10, but also the backside. By imaging also the backside of the container 10 opposite the entry surface of the hadron beam, further information may be gathered of the dose deposition in the phantom volume.

In the embodiment shown, a mirror 12M is configured to redirect light from the dose deposition towards the third light sensor or camera 23. Advantageously, by having the camera 23 outside a direct path of the hadron beam "B", radiation damage to the camera can be lower. In the embodiment shown, the container 10 with the phantom volume V is arranged on a movable platform, in this case movable by means of a robot arm 50. Of course also other mechanical movement mechanisms are possible. Advantageously, the phantom volume V can be carefully arranged in the hadron beam B, thus improving reproducibility. In the embodiment shown, the light sensors 21,22,23 are arranged on the same platform as the container 10 holding the phantom volume V.

Advantageously, a relative position of the cameras can be fixed with respect to the phantom volume V, thus further improving reproducibility.

For the purpose of clarity and a concise description, features are described herein as part of the same or separate embodiments, however, it will be appreciated that the scope of the invention may include

embodiments having combinations of all or some of the features described. For example, while embodiments were shown for verification of a treatment plan, also alternative ways may be envisaged by those skilled in the art having the benefit of the present disclosure for achieving a similar function and result. E.g. optical and electrical components, e.g. controls, may be combined or split up into one or more alternative components. The various elements of the embodiments as discussed and shown offer certain advantages, such as providing a fast and easy verification of a treatment plan. Of course, it is to be appreciated that any one of the above

embodiments or processes may be combined with one or more other embodiments or processes to provide even further improvements in finding and matching designs and advantages. It is appreciated that this disclosure offers particular advantages to quality assurance of a treatment plan, and in general can be applied for any application wherein a dose deposition needs to be measured.

While the present systems and methods have been described in particular detail with reference to specific exemplary embodiments thereof, it should also be appreciated that numerous modifications and alternative embodiments may be devised by those having ordinary skill in the art without departing from the scope of the present disclosure. For example, embodiments wherein devices or systems are disclosed to be arranged and/or constructed for performing a specified method or function inherently disclose the method or function as such and/or in combination with other disclosed embodiments of methods or systems. Furthermore, embodiments of methods are considered to inherently disclose their implementation in respective hardware, where possible, in combination with other disclosed embodiments of methods or systems. Furthermore, methods that can be embodied as program instructions, e.g. on a non-transient computer- readable storage medium, are considered inherently disclosed as such embodiment.

Finally, the above-discussion is intended to be merely illustrative of the present systems and/or methods and should not be construed as limiting the appended claims to any particular embodiment or group of embodiments. The specification and drawings are accordingly to be regarded in an illustrative manner and are not intended to limit the scope of the appended claims. In interpreting the appended claims, it should be understood that the word "comprising" does not exclude the presence of other elements or acts than those listed in a given claim; the word "a" or "an" preceding an element does not exclude the presence of a plurality of such elements; any reference signs in the claims do not limit their scope; several "means" may be represented by the same or different item(s) or implemented structure or function; any of the disclosed devices or portions thereof may be combined together or separated into further portions unless specifically stated otherwise. The mere fact that certain measures are recited in mutually different claims does not indicate that a combination of these measures cannot be used to advantage. In particular, all working combinations of the claims are considered inherently disclosed.

Claims

1. An imaging method for verification of a treatment plan (A), the imaging method comprising

- providing a phantom volume (V) consisting of a material (10m) having dose absorbing properties similar to a biological tissue according to the treatment plan (A);

- setting dose parameters (Q) of a hadron beam (B) according to the treatment plan (A);

- directing the hadron beam (B) according to the dose parameters (Q) into the phantom volume (V);

- measuring light (L) emitted from the phantom volume (V); and

- calculating a dose distribution (D) of the hadron beam (B) in the phantom volume (V) based on the measured light (L) from the phantom volume (V);

- wherein the light (L) is measured by imaging a lateral side (14,15) of the phantom volume (V) which lateral side (14, 15) has a surface normal transverse to a propagation direction (Z) of the hadron beam (B); and

- characterized in that the material (10m) of the phantom volume (V) comprises at least 98 mass percent water.

2. The method according to claim 1, wherein the material (10m) of the phantom volume (V) essentially consists of water, wherein the measured light emitted from the phantom volume (V) is generated by interaction of the hadron beam (B) with the water itself.

3. The method according to claim 1, wherein the material (10m) of the phantom volume (V) comprises between 0.01 and 2 mass percent of a fluorophore (F) for converting ultraviolet light, resulting from dose deposition by the hadron beam in the water, into visible light.

4. The method according to claim 3, wherein the fluorophore (F) comprises quinine.

5. The method according to any of the preceding claims, wherein the hadron beam (B) comprises a particle energy ( I p I ) below a threshold for hadrons directly generating Cerenkov radiation in the material (10m) of the phantom volume (V).

6. The method according to any of the preceding claims, wherein at least 90 percent of the measured light (L) is isotropically emitted light originating from within 0.1 millimeter of the deposited dose (D) by the hadron beam (B) in the material (10m) of the phantom volume (V).

7. The method according to any of the preceding claims, wherein the light (L) is measured by a light sensor (21,22) outside the phantom volume (V), wherein a lateral side (14, 15) of the phantom volume (V) is in a light path (Lx,Ly) between a deposited dose (D) of the hadron beam (B) and the light sensor (21,22).

8. The method according to any of the preceding claims, wherein the material (10m) of the phantom volume (V) is held by a container (10) comprising

- an entry surface (11) configured to receive the hadron beam (B); - a back surface (12) opposite the entry surface (11); and

- lateral surfaces (13, 14, 15, 16) connecting the entry surface (11) to the back surface (12), wherein at least one (14, 15) of the lateral surfaces (13, 14, 15, 16) is transparent to the measured light (L) for recording a lateral image (ΧΖ,ΥΖ) of the light (Lx, Ly) there through.

9. The method according to claim 8, wherein two lateral images

(ΧΖ,ΥΖ) of the light (Lx, Ly) are recorded via two transversely oriented surfaces (14, 15) of the container (10).

10. The method according to claim 8 or 9, wherein the surfaces

(11, 12, 13, 16) not used for recording the lateral image (ΧΖ,ΥΖ) are configured to reflect less than 1 percent of the measured light (L).

11. The method according to any of the preceding claims, wherein a lateral image (YZ) is recorded via a mirror (14M) in a light path (Lx) between a lateral surface (14) and the light sensor (21).

12. The method according to any of the preceding claims, further comprising providing an ionization chamber (40) in the phantom volume (V), and moving the ionization chamber (40) between

- a parked position (P0), wherein the ionization chamber (40) is outside a location where the dose distribution (D) is deposited, wherein the dose distribution (D) is measured by the light sensor (21,22); and

- a calibration position (PI), wherein the ionization chamber (40) is measures the dose distribution (D).

13. The method according to any of the preceding claims, wherein the hadron beam is a proton beam.

14. A system (100) for verification of a treatment plan (A), the system comprising

- a phantom volume (V) consisting of a material (10m) having dose absorbing properties similar to a biological tissue according to the treatment plan (A);

- a beam controller configured to control a hadron beam source and programmed for

o providing a hadron beam (B) with dose parameters (Q) according to the treatment plan (A); and

o directing the hadron beam (B) according to the dose parameters (Q) into the phantom volume (V);

- a light sensor (21,22) for measuring light (L) emitted from the phantom volume (V); and

- a dose analyser (30) configured to receive measurements from the light sensor (21,22) and programmed for calculating a dose distribution of the hadron beam (B) in the phantom volume (V) based on the measured light (L) from the phantom volume (V); - wherein the light sensor (21,22) is configured to image a lateral side (14, 15) of the phantom volume (V) which lateral side (14,15) has a surface normal that is transverse to a propagation direction (Z) of the hadron beam (B); and

15. The system according to claim 14, further comprising an ionization chamber (40) movable between

- a calibration position (PI), wherein the ionization chamber (40) is configured to measure the dose distribution (D).