Very High Energy Electrons (VHEE) of 50 - 250 MeV are an attractive choice for FLASH radiation therapy (RT). Before VHEE-FLASH RT can be considered for clinical use, a reliable dosimetric and beam monitoring system needs to be developed, able to measure the dose delivered to the patient in real-time and cut off the beam in the event of a machine fault to prevent overdosing the patient. Ionisation chambers are the standard monitors in conventional RT; however, their response saturates at the high dose rates required for FLASH. Therefore, a new dosimetry method is needed that can provide reliable measurements of the delivered dose in these conditions. Experiments using 200 MeV electrons were done at the CLEAR facility at CERN to investigate the properties of detectors such as diamond beam loss detectors, GEM foil detectors, and Timepix3 ASIC chips. From the tests, the GEM foil proved to be the most promising

Bateman, J. J.

Burrows, P. N.

Corsini, R.

Dosanjh, M.

Dyks, L. A.

Farabolini, W.

Gerbershagen, A.

Heracleous, N.

Korysko, P.

Morales, S.

Murtas, F.

Rieker, V. F.

Salvachua, B.

Silari, M.

Zorloni, G.

English

University of Groningen

   University of GroningenTesting the Properties of Beam-Dose Monitors for VHEE-FLASH Radiation TherapyBateman, J. J.; Burrows, P. N.; Dosanjh, M.; Dyks, L. A.; Korysko, P.; Corsini, R.; Farabolini,W.; Gerbershagen, A.; Heracleous, N.; Morales, S.Published in:IPAC 2022 - International Particle Accelerator Conference 2022DOI:10.18429/JACoW-IPAC2022-THPOMS029IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2022Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Bateman, J. J., Burrows, P. N., Dosanjh, M., Dyks, L. A., Korysko, P., Corsini, R., Farabolini, W.,Gerbershagen, A., Heracleous, N., Morales, S., Murtas, F., Rieker, V. F., Salvachua, B., Silari, M., &Zorloni, G. (2022). Testing the Properties of Beam-Dose Monitors for VHEE-FLASH Radiation Therapy. InIPAC 2022 - International Particle Accelerator Conference 2022 (pp. 3018-3021)https://doi.org/10.18429/JACoW-IPAC2022-THPOMS029CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 15-02-2023TESTING THE PROPERTIES OF BEAM-DOSE MONITORS FORVHEE-FLASH RADIATION THERAPYJ. J. Bateman∗, P. N. Burrows, M. Dosanjh1, L. A Dyks1, P. Korysko1,JAI, University of Oxford, Oxford, UKR. Corsini, W. Farabolini, A. Gerbershagen3, N. Heracleous, S. Morales, F. Murtas,V. F. Rieker, B. Salvachua, M. Silari, G. Zorloni, CERN, Geneva, Switzerland1also at CERN, Geneva, Switzerland2 also at PARTREC, University of Groningen, Groningen, NetherlandsAbstractVery High Energy Electrons (VHEE) of 50 - 250 MeV arean attractive choice for FLASH radiation therapy (RT). Be-fore VHEE-FLASH RT can be considered for clinical use,a reliable dosimetric and beam monitoring system needsto be developed, able to measure the dose delivered to thepatient in real-time and cut off the beam in the event of amachine fault to prevent overdosing the patient. Ionisationchambers are the standard monitors in conventional RT; how-ever, their response saturates at the high dose rates requiredfor FLASH. Therefore, a new dosimetry method is neededthat can provide reliable measurements of the delivered dosein these conditions. Experiments using 200 MeV electronswere done at the CLEAR facility at CERN to investigate theproperties of detectors such as diamond beam loss detectors,GEM foil detectors, and Timepix3 ASIC chips. From thetests, the GEM foil proved to be the most promising.INTRODUCTIONThe most widely used modality of RT is external beamtherapy with high energy photons (6 - 15 MV) and low en-ergy electrons (3 - 25 MeV). However, the maximum dosethat can be delivered to the tumour is limited by the dose thatthe surrounding healthy tissue can tolerate. This is a particu-lar challenge as these X- rays deliver their maximum dose at1.5 - 3.0 cm depth in water-equivalent tissue and then havea near-exponential attenuation. Recent research suggeststhat delivering the prescribed dose to the patient’s tumourat ultra-high dose rates (UHDR) elicits a larger differentialresponse between the tumour cells and the healthy tissues,known as the FLASH effect [1]. The entire prescribed doseis delivered within less than a second at a mean dose rate of≥ 100 Gy/s; compared to ≤ 0.03 Gy/s used in conventionalRT. Due to recent advances in particle accelerator technol-ogy such as high gradient electron acceleration cavities, e.g.the ones developed as part of the CLIC study [2], it may bepossible to treat deep-seated tumours with Very High EnergyElectrons (VHEE) with energies of 50 - 250 MeV due to theirincreased longitudinal range and sharper lateral penumbra incomparison to current clinical electron beams [3]. Ionisationchambers have been the standard for electron beam dosime-try, however, studies have shown that at the ultra high doserates required for FLASH-RT the response of the ionisation∗ joseph.bateman@physics.ox.ac.ukchamber suffers from non-linearities due to ion recombina-tion within the cavity volume [4]. Therefore, new detectorsand monitoring systems will need to be developed and testedin order to achieve accurate and reliable measurements ofthe delivered dose at UHDR for FLASH irradiations in bothpre-clinical experiments to verify the FLASH effect, and forthe eventual clinical implementation of FLASH-RT [5]. Therequirements on such a system are:• A response that does not saturate at the ultra-high doserates of ≥100 Gy/s that are required for FLASH.• A temporal resolution which is high enough to resolveindividual bunches or trains.• A response time that is fast enough to trigger a safetyinterlock in between pulses.• Minimal perturbation on the beam.The aim of the experiments described in this work is tounderstand the characteristics of the response of the detectorstested to the electron beam parameters at the CLEAR facility[6] and whether they exhibit any of the characteristics thatsuggest they would meet the criteria required for real-timedosimetry of VHEE at UHDR.PCVD DIAMOND DETECTORThe first detector tested was a B2-HV pCVD diamondbeam loss detector which is currently employed as a fastbeam loss monitor (BLM) at the LHC [7]. The diamonddetector consists of a 10 mm × 10 mm × 0.5 mm pCVDdiamond substrate coated on each side with a 200 nm thickgold electrode with a size of 8 mm × 8 mm. In the LHC, thedetector is used alongside an AD-DC splitter and a 2 GHzamplifier, however for the FLASH dosimetry experimentsonly the detector was used since the beam intensity doesnot need amplification. This detector was considered due toits known ability to have a quick response time and resolveindividual bunches when used as a BLM. However, sinceits primary usage is as a BLM and hence it is not directlyinstalled in the path of the beam center, it has been expectedthat the detector response would reach saturation at FLASHrates.SetupThe diamond detector was installed at the In-Air TestStand at CLEAR, at approximately 25 cm away from theend of the beam pipe, and was aligned such that the pCVD13th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029THPOMS029ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOI3018MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical Applicationsdiamond was on the axis of the beam. It was installed just be-hind an integrated current transformer (ICT) which was usedto measure the delivered charge. The tests on the diamonddetector were primarily to determine the beam intensities atwhich the response saturated.Results and DiscussionThe initial bias voltage for the detector was set to its nom-inal value of 500 V. The beam energy used was 200 MeV.The initial charge used was 40 pC per bunch, however for justone bunch, this was already causing the detector response tosaturate. The applied bias voltage was then adjusted downuntil the response no longer saturated which was at a voltage160 V. For the remainder of the irradiations, one bunch perpulse was used, whilst the charge per bunch was increased.Then the bias voltage was altered to a value at which thesignal no longer saturated. The results are shown in Table1. A bias voltage of 17 V was required for an unsaturatedTable 1: pCVD Diamond Detector Response SaturationValuesBunch Charge Bias Voltage at Saturation40 pC 160 V60 pC 30 V80 pC 17 Vresponse for a single bunch of 80 pC, but this led to a weaksignal with a stretched out FWHM. Furthermore, at such alow bias voltage the detector has a much lower response timeand resolving ability due to a drop in the collection efficiencyof the electrodes, hence it would not be suitable for use atsuch a low voltage [8]. Therefore, from these initial studiesit can be determined that the B2-HV pCVD Diamond BeamLoss Detector, as expected, would not be suitable as a real-time dosimeter for beam monitoring with UHDR VHEEbeams for FLASH RT. This result is in agreement with otherstudies which show this diamond detector only has a linearresponse in the range 0.01 pC - 0.06 pC [8]. For ionizingelectrons, a charge of 1 nC deposits a dose of 2 Gy in 1 cm3of water. Therefore, at the highest pulse repetition frequency(p.r.f) at CLEAR - 10 Hz [6], this equates to the diamonddetector saturating at an average dose rate of 1.6 Gy/s, sowould not be feasible for FLASH-RT.GEM FOIL DETECTORThe second detector tested was a Gas Electron Multiplier(GEM) Foil Detector. The detector consists of a thin polymerfoil, which is pierced with a high density of holes, and sand-wiched between two thin sheets of metal, clad to each face.The electric field in the pierced holes creates an avalancheof multiplied electrons upon interactions from the incomingradiation with the gas on one side of the structure, whichthen transfer to a collection region [9].SetupThe GEM foil in the detector used for this experiment hadan active area of 5 mm × 5 mm and consisted of a foil 50 𝜇mthick of kapton pierced with holes of 30 𝜇m diameter andclad with 5 𝜇m thick sheets of copper. It was positionedapproximately 40 cm away from the exit of the beam pipe atthe In-Air Test Stand of CLEAR. These tests were to deter-mine the beam intensities at which the response saturated, aswell as the detector’s resolving ability and the perturbationit has on the beam.Results and DiscussionAll of the irradiations were done at a beam energy of200 MeV. The first set of tests were with a charge of 50 pCper bunch at 1, 10, 50 and 100 bunches per train, respectively.The results showed that at these intensities the detector re-sponse does not saturate and has some temporal resolvingability on the bunches within the train. A subsequent setof irradiations was done with 100 pC per bunch with trainsof 1, 10, 50 and 100 bunches, respectively. The responseof the latter is shown in Fig. 1, and shows that at 10 nC pertrain (i.e. 100 pC per bunch with 100 bunches per train), theresponse of the GEM foil detector does not saturate. Thisequates to an average dose rate of 200 Gy/s at a 10 Hz p.r.fand therefore could be compatible with the UHDR requiredfor FLASH-RT.Figure 1: Signal detected from GEM foil with 5 mm × 5 mmactive area for 100 bunches per train and a charge of 100 pCper bunch.The temporal resolving ability of the GEM foil detectorcan be seen in Fig. 2. Here, the response of the detector tothe individual bunches can be seen (the CLEAR electronbunch spacing was 666 ps [6]).To measure the perturbation the detector had on the beam,the intensity and size of the beam was measured by a scintil-lating YAG screen 30 cm downstream of the detector, bothwith and without the detector inserted in the path of the beam.The measurements showed that the GEM foil detector scat-tered the beam to increase its size by 2.4 ×, and decreasedthe intensity of the beam by 38%.These initial results from the GEM foil detector arepromising as it shows that the response of detector doesnot saturate at charges of up to 10 nC per train. The resultsshow that the detector is also able to resolve the buncheswithin the train, and appears to have slight perturbations onthe beam.13th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical ApplicationsTHPOMS0293019ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOIFigure 2: Signal detected from GEM foil for 100 bunchesper train and a charge of 100 pC per bunch over a shortertimescale to observe resolving ability.TIMEPIX3 ASICA Timepix3 Application-Specific Integrated Circuit(ASIC) readout chip was also tested. Timepix3 is a hybridpixel detector readout chip which can record the time-of-arrival (ToA) and time-over-threshold (ToT) in each pixel[10]. The ASIC was used bare without a solid-state orgaseous sensor mounted as it was theorised that the intensi-ties from the UHDR beam required for FLASH irradiationswould be high enough to activate the readout pixels.SetupThe Timepix3 ASIC was also installed at the CLEARIn-Air Test Stand at a distance of around 50 cm from theexit of the beam pipe. The detector consists of four Timepixchips which together provide a 512 × 512 array of pixelsand a total sensitive area of 28 mm × 28 mm. The beam wastargeted onto one of the four Timepix quad chips, in whichthe response was measured. The tests were to determine thebeam intensities at which the response saturated. The mea-surements were carried out with the detector in ”Medipix”mode, in which all of the incoming particles are counted andin ToT mode, in which the incoming particles are measuredwith an incrementing counter as long as the signal is overthe threshold [11].Results and DiscussionThe response was measured for a beam energy of 200 MeVat three different beam intensities, 50 pC per train (1 bunchper train), 100 pC per train (5 bunches per train, 20 pC perbunch) and 250 pC per train (5 bunches per train, 50 pC perbunch). The response of the detector in ToT mode to the100 pC train and the 250 pC train can be seen in Fig. 3 a)and b), respectively. As can be seen in Fig. 3b), the responseof the detector already saturates at 250 pC per train, andwould hence be unsuitable for the detection of any largerintensities. This saturation was also seen at the same beamintensity when measuring the response in ”Medipix” mode.This is equivalent to an average dose rate of 5 Gy/s for a10 HZ p.r.f, therefore confirming the detector would saturateat UHDR conditions required for FLASH-RT. Whilst theresponse of the detector had saturated at these beam inten-sities, a measurement of the response of the detector afterthe experiment to no beam showed that the detector was notdamaged by the irradiations.Figure 3: Pixel intensity response of Timepix3 ASIC to: a)5 bunches of 20 pC per bunch, and b) 5 bunches of 50 pCper bunch, in ToT mode (X = Radiation Signal [a.u]).CONCLUSIONSThe aim of the experiments described in this work wasto determine whether the pCVD diamond detector, GEMfoil detector or Timepix3 ASIC exhibited the properties re-quired for real-time dosimetry for VHEE beams at UHDRrequired for FLASH RT. We concluded that neither the di-amond detector nor the Timepix3 ASIC would be suitablefor such use, since their response saturated at a charge pertrain of 80 pC and 250 pC, respectively. Considering thedose deposited in 1 cm3 of water, this corresponds to doserates of 1.6 Gy/s for the diamond detector and 5 Gy/s for theTimepix3 ASIC, demonstrating neither are able to operate atthe dose rates required for FLASH-RT. Conversely, the GEMfoil detector exhibited promising results since its responsedid not saturate at the highest charge per train used, 10 nC,which equates to a dose rate of 200 Gy/s. Hence showingthat it would be able to operate at the dose rates requiredfor FLASH-RT. Furthermore, this detector was able to showthe bunch spacing within the train, and was demonstratedto have a slight perturbation on the beam. However, furthertests would be need to be conducted on the GEM foil detectorto determine whether it’s fully suitable for use as beam-dosemonitor for FLASH RT using VHEE at UHDR, such as itsbehaviour with the larger beam sizes required for RT.REFERENCES[1] V. Favaudon et al., “Ultrahigh dose-rate FLASH irradiationincreases the differential response between normal and tu-mor tissue in mice”, Science Translational Medicine, vol. 6.,p. 245ra93, 2014. doi:10.1126/scitranslmed.3008973[2] The CLIC collaboration, the CLICdp collaboration,T. K. Charles, P. J. Giansiracusa, T. G. Lucas, R. P. Rassoolet al., “The Compact Linear 𝑒+𝑒− Collider (CLIC) - 2018Summary Report”, CERN Yellow Rep.Monogr., 2018.https://doi.org/10.48550/arXiv.1812.06018[3] C. DesRosiers et al., “150-250 MeV electron beams in radia-tion therapy”, Physics in Medicine and Biology, vol. 45, no. 7.p. 1781. 2000. doi:10.1088/0031-9155/45/7/306[4] M. McManus et al., “The challenge of ionisation chamberdosimetry in ultra-short pulsed high dose-rate Very High13th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029THPOMS029ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOI3020MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical ApplicationsEnergy Electron beams”, Scientific Reports, vol. 10, no. 1,p. 9089, 2020. doi:10.1038/s41598-020-65819-y[5] A. Vignati et al., “Beam Monitors for Tomorrow: The Chal-lenges of Electron and Photon FLASH RT”, Frontiers inPhysics, vol. 8, p. 375, 2020. doi:10.3389/fphy.2020.00375[6] K. N. Sjobak et al., “Status of the CLEAR ElectronBeam User Facility at CERN”, in Proc. IPAC’19, Mel-bourne, Australia, May 2019, pp. 983–986. doi:10.18429/JACoW-IPAC2019-MOPTS054[7] E. Griesmayer, B. Dehning, D. Dobos, E. Effinger, and H.Pernegger, “A Fast CVD Diamond Beam Loss Monitor forLHC”, in Proc. DIPAC’11, Hamburg, Germany, May 2011,paper MOPD41, pp. 143–145.[8] F. Burkart, R. Schmidt, O. Stein, D. Wollmann, and E. Gries-mayer, “Experimental Results from the Characterization ofDiamond Particle Detectors with a High Intensity ElectronBeam”, in Proc. IPAC’14, Dresden, Germany, Jun. 2014, pp.3671–3673. doi:10.18429/JACoW-IPAC2014-THPME172[9] F. Sauli, “The gas electron multiplier (GEM): Operating prin-ciples and applications”, Nuclear Instruments and Methodsin Physics Research, Section A: Accelerators, Spectrometers,Detectors and Associated Equipment, vol. 805, pp. 2-24, 2016.doi.org/10.1016/j.nima.2015.07.060[10] T. Poikela et al., “Timepix3: A 65K channel hybrid pixelreadout chip with simultaneous ToA/ToT and sparse readout”,Journal of Instrumentation, vol. 9, no. 5, p.C05013, 2014.doi:10.1088/1748-0221/9/05/C05013[11] E. Frojdh et al., “Timepix3: First measurements and charac-terization of a hybrid-pixel detector working in event drivenmode”, Journal of Instrumentation, vol. 10, no. 1, p. C01039,2015. doi:10.1088/1748-0221/10/01/C0103913th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical ApplicationsTHPOMS0293021ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOI

Testing the Properties of Beam-Dose Monitors for VHEE-FLASH Radiation Therapy

Dissertations of the University of Groningen

   University of GroningenTesting the Properties of Beam-Dose Monitors for VHEE-FLASH Radiation TherapyBateman, J. J.; Burrows, P. N.; Dosanjh, M.; Dyks, L. A.; Korysko, P.; Corsini, R.; Farabolini,W.; Gerbershagen, A.; Heracleous, N.; Morales, S.Published in:IPAC 2022 - International Particle Accelerator Conference 2022DOI:10.18429/JACoW-IPAC2022-THPOMS029IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2022Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Bateman, J. J., Burrows, P. N., Dosanjh, M., Dyks, L. A., Korysko, P., Corsini, R., Farabolini, W.,Gerbershagen, A., Heracleous, N., Morales, S., Murtas, F., Rieker, V. F., Salvachua, B., Silari, M., &Zorloni, G. (2022). Testing the Properties of Beam-Dose Monitors for VHEE-FLASH Radiation Therapy. InIPAC 2022 - International Particle Accelerator Conference 2022 (pp. 3018-3021)https://doi.org/10.18429/JACoW-IPAC2022-THPOMS029CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 10-03-2023TESTING THE PROPERTIES OF BEAM-DOSE MONITORS FORVHEE-FLASH RADIATION THERAPYJ. J. Bateman∗, P. N. Burrows, M. Dosanjh1, L. A Dyks1, P. Korysko1,JAI, University of Oxford, Oxford, UKR. Corsini, W. Farabolini, A. Gerbershagen3, N. Heracleous, S. Morales, F. Murtas,V. F. Rieker, B. Salvachua, M. Silari, G. Zorloni, CERN, Geneva, Switzerland1also at CERN, Geneva, Switzerland2 also at PARTREC, University of Groningen, Groningen, NetherlandsAbstractVery High Energy Electrons (VHEE) of 50 - 250 MeV arean attractive choice for FLASH radiation therapy (RT). Be-fore VHEE-FLASH RT can be considered for clinical use,a reliable dosimetric and beam monitoring system needsto be developed, able to measure the dose delivered to thepatient in real-time and cut off the beam in the event of amachine fault to prevent overdosing the patient. Ionisationchambers are the standard monitors in conventional RT; how-ever, their response saturates at the high dose rates requiredfor FLASH. Therefore, a new dosimetry method is neededthat can provide reliable measurements of the delivered dosein these conditions. Experiments using 200 MeV electronswere done at the CLEAR facility at CERN to investigate theproperties of detectors such as diamond beam loss detectors,GEM foil detectors, and Timepix3 ASIC chips. From thetests, the GEM foil proved to be the most promising.INTRODUCTIONThe most widely used modality of RT is external beamtherapy with high energy photons (6 - 15 MV) and low en-ergy electrons (3 - 25 MeV). However, the maximum dosethat can be delivered to the tumour is limited by the dose thatthe surrounding healthy tissue can tolerate. This is a particu-lar challenge as these X- rays deliver their maximum dose at1.5 - 3.0 cm depth in water-equivalent tissue and then havea near-exponential attenuation. Recent research suggeststhat delivering the prescribed dose to the patient’s tumourat ultra-high dose rates (UHDR) elicits a larger differentialresponse between the tumour cells and the healthy tissues,known as the FLASH effect [1]. The entire prescribed doseis delivered within less than a second at a mean dose rate of≥ 100 Gy/s; compared to ≤ 0.03 Gy/s used in conventionalRT. Due to recent advances in particle accelerator technol-ogy such as high gradient electron acceleration cavities, e.g.the ones developed as part of the CLIC study [2], it may bepossible to treat deep-seated tumours with Very High EnergyElectrons (VHEE) with energies of 50 - 250 MeV due to theirincreased longitudinal range and sharper lateral penumbra incomparison to current clinical electron beams [3]. Ionisationchambers have been the standard for electron beam dosime-try, however, studies have shown that at the ultra high doserates required for FLASH-RT the response of the ionisation∗ joseph.bateman@physics.ox.ac.ukchamber suffers from non-linearities due to ion recombina-tion within the cavity volume [4]. Therefore, new detectorsand monitoring systems will need to be developed and testedin order to achieve accurate and reliable measurements ofthe delivered dose at UHDR for FLASH irradiations in bothpre-clinical experiments to verify the FLASH effect, and forthe eventual clinical implementation of FLASH-RT [5]. Therequirements on such a system are:• A response that does not saturate at the ultra-high doserates of ≥100 Gy/s that are required for FLASH.• A temporal resolution which is high enough to resolveindividual bunches or trains.• A response time that is fast enough to trigger a safetyinterlock in between pulses.• Minimal perturbation on the beam.The aim of the experiments described in this work is tounderstand the characteristics of the response of the detectorstested to the electron beam parameters at the CLEAR facility[6] and whether they exhibit any of the characteristics thatsuggest they would meet the criteria required for real-timedosimetry of VHEE at UHDR.PCVD DIAMOND DETECTORThe first detector tested was a B2-HV pCVD diamondbeam loss detector which is currently employed as a fastbeam loss monitor (BLM) at the LHC [7]. The diamonddetector consists of a 10 mm × 10 mm × 0.5 mm pCVDdiamond substrate coated on each side with a 200 nm thickgold electrode with a size of 8 mm × 8 mm. In the LHC, thedetector is used alongside an AD-DC splitter and a 2 GHzamplifier, however for the FLASH dosimetry experimentsonly the detector was used since the beam intensity doesnot need amplification. This detector was considered due toits known ability to have a quick response time and resolveindividual bunches when used as a BLM. However, sinceits primary usage is as a BLM and hence it is not directlyinstalled in the path of the beam center, it has been expectedthat the detector response would reach saturation at FLASHrates.SetupThe diamond detector was installed at the In-Air TestStand at CLEAR, at approximately 25 cm away from theend of the beam pipe, and was aligned such that the pCVD13th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029THPOMS029ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOI3018MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical Applicationsdiamond was on the axis of the beam. It was installed just be-hind an integrated current transformer (ICT) which was usedto measure the delivered charge. The tests on the diamonddetector were primarily to determine the beam intensities atwhich the response saturated.Results and DiscussionThe initial bias voltage for the detector was set to its nom-inal value of 500 V. The beam energy used was 200 MeV.The initial charge used was 40 pC per bunch, however for justone bunch, this was already causing the detector response tosaturate. The applied bias voltage was then adjusted downuntil the response no longer saturated which was at a voltage160 V. For the remainder of the irradiations, one bunch perpulse was used, whilst the charge per bunch was increased.Then the bias voltage was altered to a value at which thesignal no longer saturated. The results are shown in Table1. A bias voltage of 17 V was required for an unsaturatedTable 1: pCVD Diamond Detector Response SaturationValuesBunch Charge Bias Voltage at Saturation40 pC 160 V60 pC 30 V80 pC 17 Vresponse for a single bunch of 80 pC, but this led to a weaksignal with a stretched out FWHM. Furthermore, at such alow bias voltage the detector has a much lower response timeand resolving ability due to a drop in the collection efficiencyof the electrodes, hence it would not be suitable for use atsuch a low voltage [8]. Therefore, from these initial studiesit can be determined that the B2-HV pCVD Diamond BeamLoss Detector, as expected, would not be suitable as a real-time dosimeter for beam monitoring with UHDR VHEEbeams for FLASH RT. This result is in agreement with otherstudies which show this diamond detector only has a linearresponse in the range 0.01 pC - 0.06 pC [8]. For ionizingelectrons, a charge of 1 nC deposits a dose of 2 Gy in 1 cm3of water. Therefore, at the highest pulse repetition frequency(p.r.f) at CLEAR - 10 Hz [6], this equates to the diamonddetector saturating at an average dose rate of 1.6 Gy/s, sowould not be feasible for FLASH-RT.GEM FOIL DETECTORThe second detector tested was a Gas Electron Multiplier(GEM) Foil Detector. The detector consists of a thin polymerfoil, which is pierced with a high density of holes, and sand-wiched between two thin sheets of metal, clad to each face.The electric field in the pierced holes creates an avalancheof multiplied electrons upon interactions from the incomingradiation with the gas on one side of the structure, whichthen transfer to a collection region [9].SetupThe GEM foil in the detector used for this experiment hadan active area of 5 mm × 5 mm and consisted of a foil 50 𝜇mthick of kapton pierced with holes of 30 𝜇m diameter andclad with 5 𝜇m thick sheets of copper. It was positionedapproximately 40 cm away from the exit of the beam pipe atthe In-Air Test Stand of CLEAR. These tests were to deter-mine the beam intensities at which the response saturated, aswell as the detector’s resolving ability and the perturbationit has on the beam.Results and DiscussionAll of the irradiations were done at a beam energy of200 MeV. The first set of tests were with a charge of 50 pCper bunch at 1, 10, 50 and 100 bunches per train, respectively.The results showed that at these intensities the detector re-sponse does not saturate and has some temporal resolvingability on the bunches within the train. A subsequent setof irradiations was done with 100 pC per bunch with trainsof 1, 10, 50 and 100 bunches, respectively. The responseof the latter is shown in Fig. 1, and shows that at 10 nC pertrain (i.e. 100 pC per bunch with 100 bunches per train), theresponse of the GEM foil detector does not saturate. Thisequates to an average dose rate of 200 Gy/s at a 10 Hz p.r.fand therefore could be compatible with the UHDR requiredfor FLASH-RT.Figure 1: Signal detected from GEM foil with 5 mm × 5 mmactive area for 100 bunches per train and a charge of 100 pCper bunch.The temporal resolving ability of the GEM foil detectorcan be seen in Fig. 2. Here, the response of the detector tothe individual bunches can be seen (the CLEAR electronbunch spacing was 666 ps [6]).To measure the perturbation the detector had on the beam,the intensity and size of the beam was measured by a scintil-lating YAG screen 30 cm downstream of the detector, bothwith and without the detector inserted in the path of the beam.The measurements showed that the GEM foil detector scat-tered the beam to increase its size by 2.4 ×, and decreasedthe intensity of the beam by 38%.These initial results from the GEM foil detector arepromising as it shows that the response of detector doesnot saturate at charges of up to 10 nC per train. The resultsshow that the detector is also able to resolve the buncheswithin the train, and appears to have slight perturbations onthe beam.13th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical ApplicationsTHPOMS0293019ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOIFigure 2: Signal detected from GEM foil for 100 bunchesper train and a charge of 100 pC per bunch over a shortertimescale to observe resolving ability.TIMEPIX3 ASICA Timepix3 Application-Specific Integrated Circuit(ASIC) readout chip was also tested. Timepix3 is a hybridpixel detector readout chip which can record the time-of-arrival (ToA) and time-over-threshold (ToT) in each pixel[10]. The ASIC was used bare without a solid-state orgaseous sensor mounted as it was theorised that the intensi-ties from the UHDR beam required for FLASH irradiationswould be high enough to activate the readout pixels.SetupThe Timepix3 ASIC was also installed at the CLEARIn-Air Test Stand at a distance of around 50 cm from theexit of the beam pipe. The detector consists of four Timepixchips which together provide a 512 × 512 array of pixelsand a total sensitive area of 28 mm × 28 mm. The beam wastargeted onto one of the four Timepix quad chips, in whichthe response was measured. The tests were to determine thebeam intensities at which the response saturated. The mea-surements were carried out with the detector in ”Medipix”mode, in which all of the incoming particles are counted andin ToT mode, in which the incoming particles are measuredwith an incrementing counter as long as the signal is overthe threshold [11].Results and DiscussionThe response was measured for a beam energy of 200 MeVat three different beam intensities, 50 pC per train (1 bunchper train), 100 pC per train (5 bunches per train, 20 pC perbunch) and 250 pC per train (5 bunches per train, 50 pC perbunch). The response of the detector in ToT mode to the100 pC train and the 250 pC train can be seen in Fig. 3 a)and b), respectively. As can be seen in Fig. 3b), the responseof the detector already saturates at 250 pC per train, andwould hence be unsuitable for the detection of any largerintensities. This saturation was also seen at the same beamintensity when measuring the response in ”Medipix” mode.This is equivalent to an average dose rate of 5 Gy/s for a10 HZ p.r.f, therefore confirming the detector would saturateat UHDR conditions required for FLASH-RT. Whilst theresponse of the detector had saturated at these beam inten-sities, a measurement of the response of the detector afterthe experiment to no beam showed that the detector was notdamaged by the irradiations.Figure 3: Pixel intensity response of Timepix3 ASIC to: a)5 bunches of 20 pC per bunch, and b) 5 bunches of 50 pCper bunch, in ToT mode (X = Radiation Signal [a.u]).CONCLUSIONSThe aim of the experiments described in this work wasto determine whether the pCVD diamond detector, GEMfoil detector or Timepix3 ASIC exhibited the properties re-quired for real-time dosimetry for VHEE beams at UHDRrequired for FLASH RT. We concluded that neither the di-amond detector nor the Timepix3 ASIC would be suitablefor such use, since their response saturated at a charge pertrain of 80 pC and 250 pC, respectively. Considering thedose deposited in 1 cm3 of water, this corresponds to doserates of 1.6 Gy/s for the diamond detector and 5 Gy/s for theTimepix3 ASIC, demonstrating neither are able to operate atthe dose rates required for FLASH-RT. Conversely, the GEMfoil detector exhibited promising results since its responsedid not saturate at the highest charge per train used, 10 nC,which equates to a dose rate of 200 Gy/s. Hence showingthat it would be able to operate at the dose rates requiredfor FLASH-RT. Furthermore, this detector was able to showthe bunch spacing within the train, and was demonstratedto have a slight perturbation on the beam. However, furthertests would be need to be conducted on the GEM foil detectorto determine whether it’s fully suitable for use as beam-dosemonitor for FLASH RT using VHEE at UHDR, such as itsbehaviour with the larger beam sizes required for RT.REFERENCES[1] V. Favaudon et al., “Ultrahigh dose-rate FLASH irradiationincreases the differential response between normal and tu-mor tissue in mice”, Science Translational Medicine, vol. 6.,p. 245ra93, 2014. doi:10.1126/scitranslmed.3008973[2] The CLIC collaboration, the CLICdp collaboration,T. K. Charles, P. J. Giansiracusa, T. G. Lucas, R. P. Rassoolet al., “The Compact Linear 𝑒+𝑒− Collider (CLIC) - 2018Summary Report”, CERN Yellow Rep.Monogr., 2018.https://doi.org/10.48550/arXiv.1812.06018[3] C. DesRosiers et al., “150-250 MeV electron beams in radia-tion therapy”, Physics in Medicine and Biology, vol. 45, no. 7.p. 1781. 2000. doi:10.1088/0031-9155/45/7/306[4] M. McManus et al., “The challenge of ionisation chamberdosimetry in ultra-short pulsed high dose-rate Very High13th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029THPOMS029ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOI3020MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical ApplicationsEnergy Electron beams”, Scientific Reports, vol. 10, no. 1,p. 9089, 2020. doi:10.1038/s41598-020-65819-y[5] A. Vignati et al., “Beam Monitors for Tomorrow: The Chal-lenges of Electron and Photon FLASH RT”, Frontiers inPhysics, vol. 8, p. 375, 2020. doi:10.3389/fphy.2020.00375[6] K. N. Sjobak et al., “Status of the CLEAR ElectronBeam User Facility at CERN”, in Proc. IPAC’19, Mel-bourne, Australia, May 2019, pp. 983–986. doi:10.18429/JACoW-IPAC2019-MOPTS054[7] E. Griesmayer, B. Dehning, D. Dobos, E. Effinger, and H.Pernegger, “A Fast CVD Diamond Beam Loss Monitor forLHC”, in Proc. DIPAC’11, Hamburg, Germany, May 2011,paper MOPD41, pp. 143–145.[8] F. Burkart, R. Schmidt, O. Stein, D. Wollmann, and E. Gries-mayer, “Experimental Results from the Characterization ofDiamond Particle Detectors with a High Intensity ElectronBeam”, in Proc. IPAC’14, Dresden, Germany, Jun. 2014, pp.3671–3673. doi:10.18429/JACoW-IPAC2014-THPME172[9] F. Sauli, “The gas electron multiplier (GEM): Operating prin-ciples and applications”, Nuclear Instruments and Methodsin Physics Research, Section A: Accelerators, Spectrometers,Detectors and Associated Equipment, vol. 805, pp. 2-24, 2016.doi.org/10.1016/j.nima.2015.07.060[10] T. Poikela et al., “Timepix3: A 65K channel hybrid pixelreadout chip with simultaneous ToA/ToT and sparse readout”,Journal of Instrumentation, vol. 9, no. 5, p.C05013, 2014.doi:10.1088/1748-0221/9/05/C05013[11] E. Frojdh et al., “Timepix3: First measurements and charac-terization of a hybrid-pixel detector working in event drivenmode”, Journal of Instrumentation, vol. 10, no. 1, p. C01039,2015. doi:10.1088/1748-0221/10/01/C0103913th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical ApplicationsTHPOMS0293021ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOI

Proceedings - University of Groningen

   University of GroningenTesting the Properties of Beam-Dose Monitors for VHEE-FLASH Radiation TherapyBateman, J. J.; Burrows, P. N.; Dosanjh, M.; Dyks, L. A.; Korysko, P.; Corsini, R.; Farabolini,W.; Gerbershagen, A.; Heracleous, N.; Morales, S.Published in:IPAC 2022 - International Particle Accelerator Conference 2022DOI:10.18429/JACoW-IPAC2022-THPOMS029IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2022Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Bateman, J. J., Burrows, P. N., Dosanjh, M., Dyks, L. A., Korysko, P., Corsini, R., Farabolini, W.,Gerbershagen, A., Heracleous, N., Morales, S., Murtas, F., Rieker, V. F., Salvachua, B., Silari, M., &Zorloni, G. (2022). Testing the Properties of Beam-Dose Monitors for VHEE-FLASH Radiation Therapy. InIPAC 2022 - International Particle Accelerator Conference 2022 (pp. 3018-3021)https://doi.org/10.18429/JACoW-IPAC2022-THPOMS029CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 12-09-2023TESTING THE PROPERTIES OF BEAM-DOSE MONITORS FORVHEE-FLASH RADIATION THERAPYJ. J. Bateman∗, P. N. Burrows, M. Dosanjh1, L. A Dyks1, P. Korysko1,JAI, University of Oxford, Oxford, UKR. Corsini, W. Farabolini, A. Gerbershagen3, N. Heracleous, S. Morales, F. Murtas,V. F. Rieker, B. Salvachua, M. Silari, G. Zorloni, CERN, Geneva, Switzerland1also at CERN, Geneva, Switzerland2 also at PARTREC, University of Groningen, Groningen, NetherlandsAbstractVery High Energy Electrons (VHEE) of 50 - 250 MeV arean attractive choice for FLASH radiation therapy (RT). Be-fore VHEE-FLASH RT can be considered for clinical use,a reliable dosimetric and beam monitoring system needsto be developed, able to measure the dose delivered to thepatient in real-time and cut off the beam in the event of amachine fault to prevent overdosing the patient. Ionisationchambers are the standard monitors in conventional RT; how-ever, their response saturates at the high dose rates requiredfor FLASH. Therefore, a new dosimetry method is neededthat can provide reliable measurements of the delivered dosein these conditions. Experiments using 200 MeV electronswere done at the CLEAR facility at CERN to investigate theproperties of detectors such as diamond beam loss detectors,GEM foil detectors, and Timepix3 ASIC chips. From thetests, the GEM foil proved to be the most promising.INTRODUCTIONThe most widely used modality of RT is external beamtherapy with high energy photons (6 - 15 MV) and low en-ergy electrons (3 - 25 MeV). However, the maximum dosethat can be delivered to the tumour is limited by the dose thatthe surrounding healthy tissue can tolerate. This is a particu-lar challenge as these X- rays deliver their maximum dose at1.5 - 3.0 cm depth in water-equivalent tissue and then havea near-exponential attenuation. Recent research suggeststhat delivering the prescribed dose to the patient’s tumourat ultra-high dose rates (UHDR) elicits a larger differentialresponse between the tumour cells and the healthy tissues,known as the FLASH effect [1]. The entire prescribed doseis delivered within less than a second at a mean dose rate of≥ 100 Gy/s; compared to ≤ 0.03 Gy/s used in conventionalRT. Due to recent advances in particle accelerator technol-ogy such as high gradient electron acceleration cavities, e.g.the ones developed as part of the CLIC study [2], it may bepossible to treat deep-seated tumours with Very High EnergyElectrons (VHEE) with energies of 50 - 250 MeV due to theirincreased longitudinal range and sharper lateral penumbra incomparison to current clinical electron beams [3]. Ionisationchambers have been the standard for electron beam dosime-try, however, studies have shown that at the ultra high doserates required for FLASH-RT the response of the ionisation∗ joseph.bateman@physics.ox.ac.ukchamber suffers from non-linearities due to ion recombina-tion within the cavity volume [4]. Therefore, new detectorsand monitoring systems will need to be developed and testedin order to achieve accurate and reliable measurements ofthe delivered dose at UHDR for FLASH irradiations in bothpre-clinical experiments to verify the FLASH effect, and forthe eventual clinical implementation of FLASH-RT [5]. Therequirements on such a system are:• A response that does not saturate at the ultra-high doserates of ≥100 Gy/s that are required for FLASH.• A temporal resolution which is high enough to resolveindividual bunches or trains.• A response time that is fast enough to trigger a safetyinterlock in between pulses.• Minimal perturbation on the beam.The aim of the experiments described in this work is tounderstand the characteristics of the response of the detectorstested to the electron beam parameters at the CLEAR facility[6] and whether they exhibit any of the characteristics thatsuggest they would meet the criteria required for real-timedosimetry of VHEE at UHDR.PCVD DIAMOND DETECTORThe first detector tested was a B2-HV pCVD diamondbeam loss detector which is currently employed as a fastbeam loss monitor (BLM) at the LHC [7]. The diamonddetector consists of a 10 mm × 10 mm × 0.5 mm pCVDdiamond substrate coated on each side with a 200 nm thickgold electrode with a size of 8 mm × 8 mm. In the LHC, thedetector is used alongside an AD-DC splitter and a 2 GHzamplifier, however for the FLASH dosimetry experimentsonly the detector was used since the beam intensity doesnot need amplification. This detector was considered due toits known ability to have a quick response time and resolveindividual bunches when used as a BLM. However, sinceits primary usage is as a BLM and hence it is not directlyinstalled in the path of the beam center, it has been expectedthat the detector response would reach saturation at FLASHrates.SetupThe diamond detector was installed at the In-Air TestStand at CLEAR, at approximately 25 cm away from theend of the beam pipe, and was aligned such that the pCVD13th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029THPOMS029ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOI3018MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical Applicationsdiamond was on the axis of the beam. It was installed just be-hind an integrated current transformer (ICT) which was usedto measure the delivered charge. The tests on the diamonddetector were primarily to determine the beam intensities atwhich the response saturated.Results and DiscussionThe initial bias voltage for the detector was set to its nom-inal value of 500 V. The beam energy used was 200 MeV.The initial charge used was 40 pC per bunch, however for justone bunch, this was already causing the detector response tosaturate. The applied bias voltage was then adjusted downuntil the response no longer saturated which was at a voltage160 V. For the remainder of the irradiations, one bunch perpulse was used, whilst the charge per bunch was increased.Then the bias voltage was altered to a value at which thesignal no longer saturated. The results are shown in Table1. A bias voltage of 17 V was required for an unsaturatedTable 1: pCVD Diamond Detector Response SaturationValuesBunch Charge Bias Voltage at Saturation40 pC 160 V60 pC 30 V80 pC 17 Vresponse for a single bunch of 80 pC, but this led to a weaksignal with a stretched out FWHM. Furthermore, at such alow bias voltage the detector has a much lower response timeand resolving ability due to a drop in the collection efficiencyof the electrodes, hence it would not be suitable for use atsuch a low voltage [8]. Therefore, from these initial studiesit can be determined that the B2-HV pCVD Diamond BeamLoss Detector, as expected, would not be suitable as a real-time dosimeter for beam monitoring with UHDR VHEEbeams for FLASH RT. This result is in agreement with otherstudies which show this diamond detector only has a linearresponse in the range 0.01 pC - 0.06 pC [8]. For ionizingelectrons, a charge of 1 nC deposits a dose of 2 Gy in 1 cm3of water. Therefore, at the highest pulse repetition frequency(p.r.f) at CLEAR - 10 Hz [6], this equates to the diamonddetector saturating at an average dose rate of 1.6 Gy/s, sowould not be feasible for FLASH-RT.GEM FOIL DETECTORThe second detector tested was a Gas Electron Multiplier(GEM) Foil Detector. The detector consists of a thin polymerfoil, which is pierced with a high density of holes, and sand-wiched between two thin sheets of metal, clad to each face.The electric field in the pierced holes creates an avalancheof multiplied electrons upon interactions from the incomingradiation with the gas on one side of the structure, whichthen transfer to a collection region [9].SetupThe GEM foil in the detector used for this experiment hadan active area of 5 mm × 5 mm and consisted of a foil 50 𝜇mthick of kapton pierced with holes of 30 𝜇m diameter andclad with 5 𝜇m thick sheets of copper. It was positionedapproximately 40 cm away from the exit of the beam pipe atthe In-Air Test Stand of CLEAR. These tests were to deter-mine the beam intensities at which the response saturated, aswell as the detector’s resolving ability and the perturbationit has on the beam.Results and DiscussionAll of the irradiations were done at a beam energy of200 MeV. The first set of tests were with a charge of 50 pCper bunch at 1, 10, 50 and 100 bunches per train, respectively.The results showed that at these intensities the detector re-sponse does not saturate and has some temporal resolvingability on the bunches within the train. A subsequent setof irradiations was done with 100 pC per bunch with trainsof 1, 10, 50 and 100 bunches, respectively. The responseof the latter is shown in Fig. 1, and shows that at 10 nC pertrain (i.e. 100 pC per bunch with 100 bunches per train), theresponse of the GEM foil detector does not saturate. Thisequates to an average dose rate of 200 Gy/s at a 10 Hz p.r.fand therefore could be compatible with the UHDR requiredfor FLASH-RT.Figure 1: Signal detected from GEM foil with 5 mm × 5 mmactive area for 100 bunches per train and a charge of 100 pCper bunch.The temporal resolving ability of the GEM foil detectorcan be seen in Fig. 2. Here, the response of the detector tothe individual bunches can be seen (the CLEAR electronbunch spacing was 666 ps [6]).To measure the perturbation the detector had on the beam,the intensity and size of the beam was measured by a scintil-lating YAG screen 30 cm downstream of the detector, bothwith and without the detector inserted in the path of the beam.The measurements showed that the GEM foil detector scat-tered the beam to increase its size by 2.4 ×, and decreasedthe intensity of the beam by 38%.These initial results from the GEM foil detector arepromising as it shows that the response of detector doesnot saturate at charges of up to 10 nC per train. The resultsshow that the detector is also able to resolve the buncheswithin the train, and appears to have slight perturbations onthe beam.13th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical ApplicationsTHPOMS0293019ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOIFigure 2: Signal detected from GEM foil for 100 bunchesper train and a charge of 100 pC per bunch over a shortertimescale to observe resolving ability.TIMEPIX3 ASICA Timepix3 Application-Specific Integrated Circuit(ASIC) readout chip was also tested. Timepix3 is a hybridpixel detector readout chip which can record the time-of-arrival (ToA) and time-over-threshold (ToT) in each pixel[10]. The ASIC was used bare without a solid-state orgaseous sensor mounted as it was theorised that the intensi-ties from the UHDR beam required for FLASH irradiationswould be high enough to activate the readout pixels.SetupThe Timepix3 ASIC was also installed at the CLEARIn-Air Test Stand at a distance of around 50 cm from theexit of the beam pipe. The detector consists of four Timepixchips which together provide a 512 × 512 array of pixelsand a total sensitive area of 28 mm × 28 mm. The beam wastargeted onto one of the four Timepix quad chips, in whichthe response was measured. The tests were to determine thebeam intensities at which the response saturated. The mea-surements were carried out with the detector in ”Medipix”mode, in which all of the incoming particles are counted andin ToT mode, in which the incoming particles are measuredwith an incrementing counter as long as the signal is overthe threshold [11].Results and DiscussionThe response was measured for a beam energy of 200 MeVat three different beam intensities, 50 pC per train (1 bunchper train), 100 pC per train (5 bunches per train, 20 pC perbunch) and 250 pC per train (5 bunches per train, 50 pC perbunch). The response of the detector in ToT mode to the100 pC train and the 250 pC train can be seen in Fig. 3 a)and b), respectively. As can be seen in Fig. 3b), the responseof the detector already saturates at 250 pC per train, andwould hence be unsuitable for the detection of any largerintensities. This saturation was also seen at the same beamintensity when measuring the response in ”Medipix” mode.This is equivalent to an average dose rate of 5 Gy/s for a10 HZ p.r.f, therefore confirming the detector would saturateat UHDR conditions required for FLASH-RT. Whilst theresponse of the detector had saturated at these beam inten-sities, a measurement of the response of the detector afterthe experiment to no beam showed that the detector was notdamaged by the irradiations.Figure 3: Pixel intensity response of Timepix3 ASIC to: a)5 bunches of 20 pC per bunch, and b) 5 bunches of 50 pCper bunch, in ToT mode (X = Radiation Signal [a.u]).CONCLUSIONSThe aim of the experiments described in this work wasto determine whether the pCVD diamond detector, GEMfoil detector or Timepix3 ASIC exhibited the properties re-quired for real-time dosimetry for VHEE beams at UHDRrequired for FLASH RT. We concluded that neither the di-amond detector nor the Timepix3 ASIC would be suitablefor such use, since their response saturated at a charge pertrain of 80 pC and 250 pC, respectively. Considering thedose deposited in 1 cm3 of water, this corresponds to doserates of 1.6 Gy/s for the diamond detector and 5 Gy/s for theTimepix3 ASIC, demonstrating neither are able to operate atthe dose rates required for FLASH-RT. Conversely, the GEMfoil detector exhibited promising results since its responsedid not saturate at the highest charge per train used, 10 nC,which equates to a dose rate of 200 Gy/s. Hence showingthat it would be able to operate at the dose rates requiredfor FLASH-RT. Furthermore, this detector was able to showthe bunch spacing within the train, and was demonstratedto have a slight perturbation on the beam. However, furthertests would be need to be conducted on the GEM foil detectorto determine whether it’s fully suitable for use as beam-dosemonitor for FLASH RT using VHEE at UHDR, such as itsbehaviour with the larger beam sizes required for RT.REFERENCES[1] V. Favaudon et al., “Ultrahigh dose-rate FLASH irradiationincreases the differential response between normal and tu-mor tissue in mice”, Science Translational Medicine, vol. 6.,p. 245ra93, 2014. doi:10.1126/scitranslmed.3008973[2] The CLIC collaboration, the CLICdp collaboration,T. K. Charles, P. J. Giansiracusa, T. G. Lucas, R. P. Rassoolet al., “The Compact Linear 𝑒+𝑒− Collider (CLIC) - 2018Summary Report”, CERN Yellow Rep.Monogr., 2018.https://doi.org/10.48550/arXiv.1812.06018[3] C. DesRosiers et al., “150-250 MeV electron beams in radia-tion therapy”, Physics in Medicine and Biology, vol. 45, no. 7.p. 1781. 2000. doi:10.1088/0031-9155/45/7/306[4] M. McManus et al., “The challenge of ionisation chamberdosimetry in ultra-short pulsed high dose-rate Very High13th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029THPOMS029ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOI3020MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical ApplicationsEnergy Electron beams”, Scientific Reports, vol. 10, no. 1,p. 9089, 2020. doi:10.1038/s41598-020-65819-y[5] A. Vignati et al., “Beam Monitors for Tomorrow: The Chal-lenges of Electron and Photon FLASH RT”, Frontiers inPhysics, vol. 8, p. 375, 2020. doi:10.3389/fphy.2020.00375[6] K. N. Sjobak et al., “Status of the CLEAR ElectronBeam User Facility at CERN”, in Proc. IPAC’19, Mel-bourne, Australia, May 2019, pp. 983–986. doi:10.18429/JACoW-IPAC2019-MOPTS054[7] E. Griesmayer, B. Dehning, D. Dobos, E. Effinger, and H.Pernegger, “A Fast CVD Diamond Beam Loss Monitor forLHC”, in Proc. DIPAC’11, Hamburg, Germany, May 2011,paper MOPD41, pp. 143–145.[8] F. Burkart, R. Schmidt, O. Stein, D. Wollmann, and E. Gries-mayer, “Experimental Results from the Characterization ofDiamond Particle Detectors with a High Intensity ElectronBeam”, in Proc. IPAC’14, Dresden, Germany, Jun. 2014, pp.3671–3673. doi:10.18429/JACoW-IPAC2014-THPME172[9] F. Sauli, “The gas electron multiplier (GEM): Operating prin-ciples and applications”, Nuclear Instruments and Methodsin Physics Research, Section A: Accelerators, Spectrometers,Detectors and Associated Equipment, vol. 805, pp. 2-24, 2016.doi.org/10.1016/j.nima.2015.07.060[10] T. Poikela et al., “Timepix3: A 65K channel hybrid pixelreadout chip with simultaneous ToA/ToT and sparse readout”,Journal of Instrumentation, vol. 9, no. 5, p.C05013, 2014.doi:10.1088/1748-0221/9/05/C05013[11] E. Frojdh et al., “Timepix3: First measurements and charac-terization of a hybrid-pixel detector working in event drivenmode”, Journal of Instrumentation, vol. 10, no. 1, p. C01039,2015. doi:10.1088/1748-0221/10/01/C0103913th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical ApplicationsTHPOMS0293021ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOI

Bateman, Joseph

Burrows, Philip

Corsini, Roberto

Dosanjh, Manjit

Dyks, Luke

Farabolini, Wilfrid

Gerbershagen, Alexander

Heracleous, Natalie

Korysko, Pierre

Morales Vigo, Sara

Murtas, Fabrizio

Rieker, Vilde

Salvachúa, Belen

Silari, Marco

Zorloni, Gabriele

CERN Document Server

ARTS repository - University of Groningen

   University of GroningenTesting the Properties of Beam-Dose Monitors for VHEE-FLASH Radiation TherapyBateman, J. J.; Burrows, P. N.; Dosanjh, M.; Dyks, L. A.; Korysko, P.; Corsini, R.; Farabolini,W.; Gerbershagen, A.; Heracleous, N.; Morales, S.Published in:IPAC 2022 - International Particle Accelerator Conference 2022DOI:10.18429/JACoW-IPAC2022-THPOMS029IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2022Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Bateman, J. J., Burrows, P. N., Dosanjh, M., Dyks, L. A., Korysko, P., Corsini, R., Farabolini, W.,Gerbershagen, A., Heracleous, N., Morales, S., Murtas, F., Rieker, V. F., Salvachua, B., Silari, M., &Zorloni, G. (2022). Testing the Properties of Beam-Dose Monitors for VHEE-FLASH Radiation Therapy. InIPAC 2022 - International Particle Accelerator Conference 2022 (pp. 3018-3021)https://doi.org/10.18429/JACoW-IPAC2022-THPOMS029CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 01-11-2023TESTING THE PROPERTIES OF BEAM-DOSE MONITORS FORVHEE-FLASH RADIATION THERAPYJ. J. Bateman∗, P. N. Burrows, M. Dosanjh1, L. A Dyks1, P. Korysko1,JAI, University of Oxford, Oxford, UKR. Corsini, W. Farabolini, A. Gerbershagen3, N. Heracleous, S. Morales, F. Murtas,V. F. Rieker, B. Salvachua, M. Silari, G. Zorloni, CERN, Geneva, Switzerland1also at CERN, Geneva, Switzerland2 also at PARTREC, University of Groningen, Groningen, NetherlandsAbstractVery High Energy Electrons (VHEE) of 50 - 250 MeV arean attractive choice for FLASH radiation therapy (RT). Be-fore VHEE-FLASH RT can be considered for clinical use,a reliable dosimetric and beam monitoring system needsto be developed, able to measure the dose delivered to thepatient in real-time and cut off the beam in the event of amachine fault to prevent overdosing the patient. Ionisationchambers are the standard monitors in conventional RT; how-ever, their response saturates at the high dose rates requiredfor FLASH. Therefore, a new dosimetry method is neededthat can provide reliable measurements of the delivered dosein these conditions. Experiments using 200 MeV electronswere done at the CLEAR facility at CERN to investigate theproperties of detectors such as diamond beam loss detectors,GEM foil detectors, and Timepix3 ASIC chips. From thetests, the GEM foil proved to be the most promising.INTRODUCTIONThe most widely used modality of RT is external beamtherapy with high energy photons (6 - 15 MV) and low en-ergy electrons (3 - 25 MeV). However, the maximum dosethat can be delivered to the tumour is limited by the dose thatthe surrounding healthy tissue can tolerate. This is a particu-lar challenge as these X- rays deliver their maximum dose at1.5 - 3.0 cm depth in water-equivalent tissue and then havea near-exponential attenuation. Recent research suggeststhat delivering the prescribed dose to the patient’s tumourat ultra-high dose rates (UHDR) elicits a larger differentialresponse between the tumour cells and the healthy tissues,known as the FLASH effect [1]. The entire prescribed doseis delivered within less than a second at a mean dose rate of≥ 100 Gy/s; compared to ≤ 0.03 Gy/s used in conventionalRT. Due to recent advances in particle accelerator technol-ogy such as high gradient electron acceleration cavities, e.g.the ones developed as part of the CLIC study [2], it may bepossible to treat deep-seated tumours with Very High EnergyElectrons (VHEE) with energies of 50 - 250 MeV due to theirincreased longitudinal range and sharper lateral penumbra incomparison to current clinical electron beams [3]. Ionisationchambers have been the standard for electron beam dosime-try, however, studies have shown that at the ultra high doserates required for FLASH-RT the response of the ionisation∗ joseph.bateman@physics.ox.ac.ukchamber suffers from non-linearities due to ion recombina-tion within the cavity volume [4]. Therefore, new detectorsand monitoring systems will need to be developed and testedin order to achieve accurate and reliable measurements ofthe delivered dose at UHDR for FLASH irradiations in bothpre-clinical experiments to verify the FLASH effect, and forthe eventual clinical implementation of FLASH-RT [5]. Therequirements on such a system are:• A response that does not saturate at the ultra-high doserates of ≥100 Gy/s that are required for FLASH.• A temporal resolution which is high enough to resolveindividual bunches or trains.• A response time that is fast enough to trigger a safetyinterlock in between pulses.• Minimal perturbation on the beam.The aim of the experiments described in this work is tounderstand the characteristics of the response of the detectorstested to the electron beam parameters at the CLEAR facility[6] and whether they exhibit any of the characteristics thatsuggest they would meet the criteria required for real-timedosimetry of VHEE at UHDR.PCVD DIAMOND DETECTORThe first detector tested was a B2-HV pCVD diamondbeam loss detector which is currently employed as a fastbeam loss monitor (BLM) at the LHC [7]. The diamonddetector consists of a 10 mm × 10 mm × 0.5 mm pCVDdiamond substrate coated on each side with a 200 nm thickgold electrode with a size of 8 mm × 8 mm. In the LHC, thedetector is used alongside an AD-DC splitter and a 2 GHzamplifier, however for the FLASH dosimetry experimentsonly the detector was used since the beam intensity doesnot need amplification. This detector was considered due toits known ability to have a quick response time and resolveindividual bunches when used as a BLM. However, sinceits primary usage is as a BLM and hence it is not directlyinstalled in the path of the beam center, it has been expectedthat the detector response would reach saturation at FLASHrates.SetupThe diamond detector was installed at the In-Air TestStand at CLEAR, at approximately 25 cm away from theend of the beam pipe, and was aligned such that the pCVD13th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029THPOMS029ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOI3018MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical Applicationsdiamond was on the axis of the beam. It was installed just be-hind an integrated current transformer (ICT) which was usedto measure the delivered charge. The tests on the diamonddetector were primarily to determine the beam intensities atwhich the response saturated.Results and DiscussionThe initial bias voltage for the detector was set to its nom-inal value of 500 V. The beam energy used was 200 MeV.The initial charge used was 40 pC per bunch, however for justone bunch, this was already causing the detector response tosaturate. The applied bias voltage was then adjusted downuntil the response no longer saturated which was at a voltage160 V. For the remainder of the irradiations, one bunch perpulse was used, whilst the charge per bunch was increased.Then the bias voltage was altered to a value at which thesignal no longer saturated. The results are shown in Table1. A bias voltage of 17 V was required for an unsaturatedTable 1: pCVD Diamond Detector Response SaturationValuesBunch Charge Bias Voltage at Saturation40 pC 160 V60 pC 30 V80 pC 17 Vresponse for a single bunch of 80 pC, but this led to a weaksignal with a stretched out FWHM. Furthermore, at such alow bias voltage the detector has a much lower response timeand resolving ability due to a drop in the collection efficiencyof the electrodes, hence it would not be suitable for use atsuch a low voltage [8]. Therefore, from these initial studiesit can be determined that the B2-HV pCVD Diamond BeamLoss Detector, as expected, would not be suitable as a real-time dosimeter for beam monitoring with UHDR VHEEbeams for FLASH RT. This result is in agreement with otherstudies which show this diamond detector only has a linearresponse in the range 0.01 pC - 0.06 pC [8]. For ionizingelectrons, a charge of 1 nC deposits a dose of 2 Gy in 1 cm3of water. Therefore, at the highest pulse repetition frequency(p.r.f) at CLEAR - 10 Hz [6], this equates to the diamonddetector saturating at an average dose rate of 1.6 Gy/s, sowould not be feasible for FLASH-RT.GEM FOIL DETECTORThe second detector tested was a Gas Electron Multiplier(GEM) Foil Detector. The detector consists of a thin polymerfoil, which is pierced with a high density of holes, and sand-wiched between two thin sheets of metal, clad to each face.The electric field in the pierced holes creates an avalancheof multiplied electrons upon interactions from the incomingradiation with the gas on one side of the structure, whichthen transfer to a collection region [9].SetupThe GEM foil in the detector used for this experiment hadan active area of 5 mm × 5 mm and consisted of a foil 50 𝜇mthick of kapton pierced with holes of 30 𝜇m diameter andclad with 5 𝜇m thick sheets of copper. It was positionedapproximately 40 cm away from the exit of the beam pipe atthe In-Air Test Stand of CLEAR. These tests were to deter-mine the beam intensities at which the response saturated, aswell as the detector’s resolving ability and the perturbationit has on the beam.Results and DiscussionAll of the irradiations were done at a beam energy of200 MeV. The first set of tests were with a charge of 50 pCper bunch at 1, 10, 50 and 100 bunches per train, respectively.The results showed that at these intensities the detector re-sponse does not saturate and has some temporal resolvingability on the bunches within the train. A subsequent setof irradiations was done with 100 pC per bunch with trainsof 1, 10, 50 and 100 bunches, respectively. The responseof the latter is shown in Fig. 1, and shows that at 10 nC pertrain (i.e. 100 pC per bunch with 100 bunches per train), theresponse of the GEM foil detector does not saturate. Thisequates to an average dose rate of 200 Gy/s at a 10 Hz p.r.fand therefore could be compatible with the UHDR requiredfor FLASH-RT.Figure 1: Signal detected from GEM foil with 5 mm × 5 mmactive area for 100 bunches per train and a charge of 100 pCper bunch.The temporal resolving ability of the GEM foil detectorcan be seen in Fig. 2. Here, the response of the detector tothe individual bunches can be seen (the CLEAR electronbunch spacing was 666 ps [6]).To measure the perturbation the detector had on the beam,the intensity and size of the beam was measured by a scintil-lating YAG screen 30 cm downstream of the detector, bothwith and without the detector inserted in the path of the beam.The measurements showed that the GEM foil detector scat-tered the beam to increase its size by 2.4 ×, and decreasedthe intensity of the beam by 38%.These initial results from the GEM foil detector arepromising as it shows that the response of detector doesnot saturate at charges of up to 10 nC per train. The resultsshow that the detector is also able to resolve the buncheswithin the train, and appears to have slight perturbations onthe beam.13th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical ApplicationsTHPOMS0293019ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOIFigure 2: Signal detected from GEM foil for 100 bunchesper train and a charge of 100 pC per bunch over a shortertimescale to observe resolving ability.TIMEPIX3 ASICA Timepix3 Application-Specific Integrated Circuit(ASIC) readout chip was also tested. Timepix3 is a hybridpixel detector readout chip which can record the time-of-arrival (ToA) and time-over-threshold (ToT) in each pixel[10]. The ASIC was used bare without a solid-state orgaseous sensor mounted as it was theorised that the intensi-ties from the UHDR beam required for FLASH irradiationswould be high enough to activate the readout pixels.SetupThe Timepix3 ASIC was also installed at the CLEARIn-Air Test Stand at a distance of around 50 cm from theexit of the beam pipe. The detector consists of four Timepixchips which together provide a 512 × 512 array of pixelsand a total sensitive area of 28 mm × 28 mm. The beam wastargeted onto one of the four Timepix quad chips, in whichthe response was measured. The tests were to determine thebeam intensities at which the response saturated. The mea-surements were carried out with the detector in ”Medipix”mode, in which all of the incoming particles are counted andin ToT mode, in which the incoming particles are measuredwith an incrementing counter as long as the signal is overthe threshold [11].Results and DiscussionThe response was measured for a beam energy of 200 MeVat three different beam intensities, 50 pC per train (1 bunchper train), 100 pC per train (5 bunches per train, 20 pC perbunch) and 250 pC per train (5 bunches per train, 50 pC perbunch). The response of the detector in ToT mode to the100 pC train and the 250 pC train can be seen in Fig. 3 a)and b), respectively. As can be seen in Fig. 3b), the responseof the detector already saturates at 250 pC per train, andwould hence be unsuitable for the detection of any largerintensities. This saturation was also seen at the same beamintensity when measuring the response in ”Medipix” mode.This is equivalent to an average dose rate of 5 Gy/s for a10 HZ p.r.f, therefore confirming the detector would saturateat UHDR conditions required for FLASH-RT. Whilst theresponse of the detector had saturated at these beam inten-sities, a measurement of the response of the detector afterthe experiment to no beam showed that the detector was notdamaged by the irradiations.Figure 3: Pixel intensity response of Timepix3 ASIC to: a)5 bunches of 20 pC per bunch, and b) 5 bunches of 50 pCper bunch, in ToT mode (X = Radiation Signal [a.u]).CONCLUSIONSThe aim of the experiments described in this work wasto determine whether the pCVD diamond detector, GEMfoil detector or Timepix3 ASIC exhibited the properties re-quired for real-time dosimetry for VHEE beams at UHDRrequired for FLASH RT. We concluded that neither the di-amond detector nor the Timepix3 ASIC would be suitablefor such use, since their response saturated at a charge pertrain of 80 pC and 250 pC, respectively. Considering thedose deposited in 1 cm3 of water, this corresponds to doserates of 1.6 Gy/s for the diamond detector and 5 Gy/s for theTimepix3 ASIC, demonstrating neither are able to operate atthe dose rates required for FLASH-RT. Conversely, the GEMfoil detector exhibited promising results since its responsedid not saturate at the highest charge per train used, 10 nC,which equates to a dose rate of 200 Gy/s. Hence showingthat it would be able to operate at the dose rates requiredfor FLASH-RT. Furthermore, this detector was able to showthe bunch spacing within the train, and was demonstratedto have a slight perturbation on the beam. However, furthertests would be need to be conducted on the GEM foil detectorto determine whether it’s fully suitable for use as beam-dosemonitor for FLASH RT using VHEE at UHDR, such as itsbehaviour with the larger beam sizes required for RT.REFERENCES[1] V. Favaudon et al., “Ultrahigh dose-rate FLASH irradiationincreases the differential response between normal and tu-mor tissue in mice”, Science Translational Medicine, vol. 6.,p. 245ra93, 2014. doi:10.1126/scitranslmed.3008973[2] The CLIC collaboration, the CLICdp collaboration,T. K. Charles, P. J. Giansiracusa, T. G. Lucas, R. P. Rassoolet al., “The Compact Linear 𝑒+𝑒− Collider (CLIC) - 2018Summary Report”, CERN Yellow Rep.Monogr., 2018.https://doi.org/10.48550/arXiv.1812.06018[3] C. DesRosiers et al., “150-250 MeV electron beams in radia-tion therapy”, Physics in Medicine and Biology, vol. 45, no. 7.p. 1781. 2000. doi:10.1088/0031-9155/45/7/306[4] M. McManus et al., “The challenge of ionisation chamberdosimetry in ultra-short pulsed high dose-rate Very High13th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029THPOMS029ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOI3020MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical ApplicationsEnergy Electron beams”, Scientific Reports, vol. 10, no. 1,p. 9089, 2020. doi:10.1038/s41598-020-65819-y[5] A. Vignati et al., “Beam Monitors for Tomorrow: The Chal-lenges of Electron and Photon FLASH RT”, Frontiers inPhysics, vol. 8, p. 375, 2020. doi:10.3389/fphy.2020.00375[6] K. N. Sjobak et al., “Status of the CLEAR ElectronBeam User Facility at CERN”, in Proc. IPAC’19, Mel-bourne, Australia, May 2019, pp. 983–986. doi:10.18429/JACoW-IPAC2019-MOPTS054[7] E. Griesmayer, B. Dehning, D. Dobos, E. Effinger, and H.Pernegger, “A Fast CVD Diamond Beam Loss Monitor forLHC”, in Proc. DIPAC’11, Hamburg, Germany, May 2011,paper MOPD41, pp. 143–145.[8] F. Burkart, R. Schmidt, O. Stein, D. Wollmann, and E. Gries-mayer, “Experimental Results from the Characterization ofDiamond Particle Detectors with a High Intensity ElectronBeam”, in Proc. IPAC’14, Dresden, Germany, Jun. 2014, pp.3671–3673. doi:10.18429/JACoW-IPAC2014-THPME172[9] F. Sauli, “The gas electron multiplier (GEM): Operating prin-ciples and applications”, Nuclear Instruments and Methodsin Physics Research, Section A: Accelerators, Spectrometers,Detectors and Associated Equipment, vol. 805, pp. 2-24, 2016.doi.org/10.1016/j.nima.2015.07.060[10] T. Poikela et al., “Timepix3: A 65K channel hybrid pixelreadout chip with simultaneous ToA/ToT and sparse readout”,Journal of Instrumentation, vol. 9, no. 5, p.C05013, 2014.doi:10.1088/1748-0221/9/05/C05013[11] E. Frojdh et al., “Timepix3: First measurements and charac-terization of a hybrid-pixel detector working in event drivenmode”, Journal of Instrumentation, vol. 10, no. 1, p. C01039,2015. doi:10.1088/1748-0221/10/01/C0103913th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical ApplicationsTHPOMS0293021ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOI

   University of GroningenTesting the Properties of Beam-Dose Monitors for VHEE-FLASH Radiation TherapyBateman, J. J.; Burrows, P. N.; Dosanjh, M.; Dyks, L. A.; Korysko, P.; Corsini, R.; Farabolini,W.; Gerbershagen, A.; Heracleous, N.; Morales, S.Published in:IPAC 2022 - International Particle Accelerator Conference 2022DOI:10.18429/JACoW-IPAC2022-THPOMS029IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2022Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Bateman, J. J., Burrows, P. N., Dosanjh, M., Dyks, L. A., Korysko, P., Corsini, R., Farabolini, W.,Gerbershagen, A., Heracleous, N., Morales, S., Murtas, F., Rieker, V. F., Salvachua, B., Silari, M., &Zorloni, G. (2022). Testing the Properties of Beam-Dose Monitors for VHEE-FLASH Radiation Therapy. InIPAC 2022 - International Particle Accelerator Conference 2022 (pp. 3018-3021)https://doi.org/10.18429/JACoW-IPAC2022-THPOMS029CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 11-09-2023TESTING THE PROPERTIES OF BEAM-DOSE MONITORS FORVHEE-FLASH RADIATION THERAPYJ. J. Bateman∗, P. N. Burrows, M. Dosanjh1, L. A Dyks1, P. Korysko1,JAI, University of Oxford, Oxford, UKR. Corsini, W. Farabolini, A. Gerbershagen3, N. Heracleous, S. Morales, F. Murtas,V. F. Rieker, B. Salvachua, M. Silari, G. Zorloni, CERN, Geneva, Switzerland1also at CERN, Geneva, Switzerland2 also at PARTREC, University of Groningen, Groningen, NetherlandsAbstractVery High Energy Electrons (VHEE) of 50 - 250 MeV arean attractive choice for FLASH radiation therapy (RT). Be-fore VHEE-FLASH RT can be considered for clinical use,a reliable dosimetric and beam monitoring system needsto be developed, able to measure the dose delivered to thepatient in real-time and cut off the beam in the event of amachine fault to prevent overdosing the patient. Ionisationchambers are the standard monitors in conventional RT; how-ever, their response saturates at the high dose rates requiredfor FLASH. Therefore, a new dosimetry method is neededthat can provide reliable measurements of the delivered dosein these conditions. Experiments using 200 MeV electronswere done at the CLEAR facility at CERN to investigate theproperties of detectors such as diamond beam loss detectors,GEM foil detectors, and Timepix3 ASIC chips. From thetests, the GEM foil proved to be the most promising.INTRODUCTIONThe most widely used modality of RT is external beamtherapy with high energy photons (6 - 15 MV) and low en-ergy electrons (3 - 25 MeV). However, the maximum dosethat can be delivered to the tumour is limited by the dose thatthe surrounding healthy tissue can tolerate. This is a particu-lar challenge as these X- rays deliver their maximum dose at1.5 - 3.0 cm depth in water-equivalent tissue and then havea near-exponential attenuation. Recent research suggeststhat delivering the prescribed dose to the patient’s tumourat ultra-high dose rates (UHDR) elicits a larger differentialresponse between the tumour cells and the healthy tissues,known as the FLASH effect [1]. The entire prescribed doseis delivered within less than a second at a mean dose rate of≥ 100 Gy/s; compared to ≤ 0.03 Gy/s used in conventionalRT. Due to recent advances in particle accelerator technol-ogy such as high gradient electron acceleration cavities, e.g.the ones developed as part of the CLIC study [2], it may bepossible to treat deep-seated tumours with Very High EnergyElectrons (VHEE) with energies of 50 - 250 MeV due to theirincreased longitudinal range and sharper lateral penumbra incomparison to current clinical electron beams [3]. Ionisationchambers have been the standard for electron beam dosime-try, however, studies have shown that at the ultra high doserates required for FLASH-RT the response of the ionisation∗ joseph.bateman@physics.ox.ac.ukchamber suffers from non-linearities due to ion recombina-tion within the cavity volume [4]. Therefore, new detectorsand monitoring systems will need to be developed and testedin order to achieve accurate and reliable measurements ofthe delivered dose at UHDR for FLASH irradiations in bothpre-clinical experiments to verify the FLASH effect, and forthe eventual clinical implementation of FLASH-RT [5]. Therequirements on such a system are:• A response that does not saturate at the ultra-high doserates of ≥100 Gy/s that are required for FLASH.• A temporal resolution which is high enough to resolveindividual bunches or trains.• A response time that is fast enough to trigger a safetyinterlock in between pulses.• Minimal perturbation on the beam.The aim of the experiments described in this work is tounderstand the characteristics of the response of the detectorstested to the electron beam parameters at the CLEAR facility[6] and whether they exhibit any of the characteristics thatsuggest they would meet the criteria required for real-timedosimetry of VHEE at UHDR.PCVD DIAMOND DETECTORThe first detector tested was a B2-HV pCVD diamondbeam loss detector which is currently employed as a fastbeam loss monitor (BLM) at the LHC [7]. The diamonddetector consists of a 10 mm × 10 mm × 0.5 mm pCVDdiamond substrate coated on each side with a 200 nm thickgold electrode with a size of 8 mm × 8 mm. In the LHC, thedetector is used alongside an AD-DC splitter and a 2 GHzamplifier, however for the FLASH dosimetry experimentsonly the detector was used since the beam intensity doesnot need amplification. This detector was considered due toits known ability to have a quick response time and resolveindividual bunches when used as a BLM. However, sinceits primary usage is as a BLM and hence it is not directlyinstalled in the path of the beam center, it has been expectedthat the detector response would reach saturation at FLASHrates.SetupThe diamond detector was installed at the In-Air TestStand at CLEAR, at approximately 25 cm away from theend of the beam pipe, and was aligned such that the pCVD13th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029THPOMS029ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOI3018MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical Applicationsdiamond was on the axis of the beam. It was installed just be-hind an integrated current transformer (ICT) which was usedto measure the delivered charge. The tests on the diamonddetector were primarily to determine the beam intensities atwhich the response saturated.Results and DiscussionThe initial bias voltage for the detector was set to its nom-inal value of 500 V. The beam energy used was 200 MeV.The initial charge used was 40 pC per bunch, however for justone bunch, this was already causing the detector response tosaturate. The applied bias voltage was then adjusted downuntil the response no longer saturated which was at a voltage160 V. For the remainder of the irradiations, one bunch perpulse was used, whilst the charge per bunch was increased.Then the bias voltage was altered to a value at which thesignal no longer saturated. The results are shown in Table1. A bias voltage of 17 V was required for an unsaturatedTable 1: pCVD Diamond Detector Response SaturationValuesBunch Charge Bias Voltage at Saturation40 pC 160 V60 pC 30 V80 pC 17 Vresponse for a single bunch of 80 pC, but this led to a weaksignal with a stretched out FWHM. Furthermore, at such alow bias voltage the detector has a much lower response timeand resolving ability due to a drop in the collection efficiencyof the electrodes, hence it would not be suitable for use atsuch a low voltage [8]. Therefore, from these initial studiesit can be determined that the B2-HV pCVD Diamond BeamLoss Detector, as expected, would not be suitable as a real-time dosimeter for beam monitoring with UHDR VHEEbeams for FLASH RT. This result is in agreement with otherstudies which show this diamond detector only has a linearresponse in the range 0.01 pC - 0.06 pC [8]. For ionizingelectrons, a charge of 1 nC deposits a dose of 2 Gy in 1 cm3of water. Therefore, at the highest pulse repetition frequency(p.r.f) at CLEAR - 10 Hz [6], this equates to the diamonddetector saturating at an average dose rate of 1.6 Gy/s, sowould not be feasible for FLASH-RT.GEM FOIL DETECTORThe second detector tested was a Gas Electron Multiplier(GEM) Foil Detector. The detector consists of a thin polymerfoil, which is pierced with a high density of holes, and sand-wiched between two thin sheets of metal, clad to each face.The electric field in the pierced holes creates an avalancheof multiplied electrons upon interactions from the incomingradiation with the gas on one side of the structure, whichthen transfer to a collection region [9].SetupThe GEM foil in the detector used for this experiment hadan active area of 5 mm × 5 mm and consisted of a foil 50 𝜇mthick of kapton pierced with holes of 30 𝜇m diameter andclad with 5 𝜇m thick sheets of copper. It was positionedapproximately 40 cm away from the exit of the beam pipe atthe In-Air Test Stand of CLEAR. These tests were to deter-mine the beam intensities at which the response saturated, aswell as the detector’s resolving ability and the perturbationit has on the beam.Results and DiscussionAll of the irradiations were done at a beam energy of200 MeV. The first set of tests were with a charge of 50 pCper bunch at 1, 10, 50 and 100 bunches per train, respectively.The results showed that at these intensities the detector re-sponse does not saturate and has some temporal resolvingability on the bunches within the train. A subsequent setof irradiations was done with 100 pC per bunch with trainsof 1, 10, 50 and 100 bunches, respectively. The responseof the latter is shown in Fig. 1, and shows that at 10 nC pertrain (i.e. 100 pC per bunch with 100 bunches per train), theresponse of the GEM foil detector does not saturate. Thisequates to an average dose rate of 200 Gy/s at a 10 Hz p.r.fand therefore could be compatible with the UHDR requiredfor FLASH-RT.Figure 1: Signal detected from GEM foil with 5 mm × 5 mmactive area for 100 bunches per train and a charge of 100 pCper bunch.The temporal resolving ability of the GEM foil detectorcan be seen in Fig. 2. Here, the response of the detector tothe individual bunches can be seen (the CLEAR electronbunch spacing was 666 ps [6]).To measure the perturbation the detector had on the beam,the intensity and size of the beam was measured by a scintil-lating YAG screen 30 cm downstream of the detector, bothwith and without the detector inserted in the path of the beam.The measurements showed that the GEM foil detector scat-tered the beam to increase its size by 2.4 ×, and decreasedthe intensity of the beam by 38%.These initial results from the GEM foil detector arepromising as it shows that the response of detector doesnot saturate at charges of up to 10 nC per train. The resultsshow that the detector is also able to resolve the buncheswithin the train, and appears to have slight perturbations onthe beam.13th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical ApplicationsTHPOMS0293019ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOIFigure 2: Signal detected from GEM foil for 100 bunchesper train and a charge of 100 pC per bunch over a shortertimescale to observe resolving ability.TIMEPIX3 ASICA Timepix3 Application-Specific Integrated Circuit(ASIC) readout chip was also tested. Timepix3 is a hybridpixel detector readout chip which can record the time-of-arrival (ToA) and time-over-threshold (ToT) in each pixel[10]. The ASIC was used bare without a solid-state orgaseous sensor mounted as it was theorised that the intensi-ties from the UHDR beam required for FLASH irradiationswould be high enough to activate the readout pixels.SetupThe Timepix3 ASIC was also installed at the CLEARIn-Air Test Stand at a distance of around 50 cm from theexit of the beam pipe. The detector consists of four Timepixchips which together provide a 512 × 512 array of pixelsand a total sensitive area of 28 mm × 28 mm. The beam wastargeted onto one of the four Timepix quad chips, in whichthe response was measured. The tests were to determine thebeam intensities at which the response saturated. The mea-surements were carried out with the detector in ”Medipix”mode, in which all of the incoming particles are counted andin ToT mode, in which the incoming particles are measuredwith an incrementing counter as long as the signal is overthe threshold [11].Results and DiscussionThe response was measured for a beam energy of 200 MeVat three different beam intensities, 50 pC per train (1 bunchper train), 100 pC per train (5 bunches per train, 20 pC perbunch) and 250 pC per train (5 bunches per train, 50 pC perbunch). The response of the detector in ToT mode to the100 pC train and the 250 pC train can be seen in Fig. 3 a)and b), respectively. As can be seen in Fig. 3b), the responseof the detector already saturates at 250 pC per train, andwould hence be unsuitable for the detection of any largerintensities. This saturation was also seen at the same beamintensity when measuring the response in ”Medipix” mode.This is equivalent to an average dose rate of 5 Gy/s for a10 HZ p.r.f, therefore confirming the detector would saturateat UHDR conditions required for FLASH-RT. Whilst theresponse of the detector had saturated at these beam inten-sities, a measurement of the response of the detector afterthe experiment to no beam showed that the detector was notdamaged by the irradiations.Figure 3: Pixel intensity response of Timepix3 ASIC to: a)5 bunches of 20 pC per bunch, and b) 5 bunches of 50 pCper bunch, in ToT mode (X = Radiation Signal [a.u]).CONCLUSIONSThe aim of the experiments described in this work wasto determine whether the pCVD diamond detector, GEMfoil detector or Timepix3 ASIC exhibited the properties re-quired for real-time dosimetry for VHEE beams at UHDRrequired for FLASH RT. We concluded that neither the di-amond detector nor the Timepix3 ASIC would be suitablefor such use, since their response saturated at a charge pertrain of 80 pC and 250 pC, respectively. Considering thedose deposited in 1 cm3 of water, this corresponds to doserates of 1.6 Gy/s for the diamond detector and 5 Gy/s for theTimepix3 ASIC, demonstrating neither are able to operate atthe dose rates required for FLASH-RT. Conversely, the GEMfoil detector exhibited promising results since its responsedid not saturate at the highest charge per train used, 10 nC,which equates to a dose rate of 200 Gy/s. Hence showingthat it would be able to operate at the dose rates requiredfor FLASH-RT. Furthermore, this detector was able to showthe bunch spacing within the train, and was demonstratedto have a slight perturbation on the beam. However, furthertests would be need to be conducted on the GEM foil detectorto determine whether it’s fully suitable for use as beam-dosemonitor for FLASH RT using VHEE at UHDR, such as itsbehaviour with the larger beam sizes required for RT.REFERENCES[1] V. Favaudon et al., “Ultrahigh dose-rate FLASH irradiationincreases the differential response between normal and tu-mor tissue in mice”, Science Translational Medicine, vol. 6.,p. 245ra93, 2014. doi:10.1126/scitranslmed.3008973[2] The CLIC collaboration, the CLICdp collaboration,T. K. Charles, P. J. Giansiracusa, T. G. Lucas, R. P. Rassoolet al., “The Compact Linear 𝑒+𝑒− Collider (CLIC) - 2018Summary Report”, CERN Yellow Rep.Monogr., 2018.https://doi.org/10.48550/arXiv.1812.06018[3] C. DesRosiers et al., “150-250 MeV electron beams in radia-tion therapy”, Physics in Medicine and Biology, vol. 45, no. 7.p. 1781. 2000. doi:10.1088/0031-9155/45/7/306[4] M. McManus et al., “The challenge of ionisation chamberdosimetry in ultra-short pulsed high dose-rate Very High13th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029THPOMS029ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOI3020MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical ApplicationsEnergy Electron beams”, Scientific Reports, vol. 10, no. 1,p. 9089, 2020. doi:10.1038/s41598-020-65819-y[5] A. Vignati et al., “Beam Monitors for Tomorrow: The Chal-lenges of Electron and Photon FLASH RT”, Frontiers inPhysics, vol. 8, p. 375, 2020. doi:10.3389/fphy.2020.00375[6] K. N. Sjobak et al., “Status of the CLEAR ElectronBeam User Facility at CERN”, in Proc. IPAC’19, Mel-bourne, Australia, May 2019, pp. 983–986. doi:10.18429/JACoW-IPAC2019-MOPTS054[7] E. Griesmayer, B. Dehning, D. Dobos, E. Effinger, and H.Pernegger, “A Fast CVD Diamond Beam Loss Monitor forLHC”, in Proc. DIPAC’11, Hamburg, Germany, May 2011,paper MOPD41, pp. 143–145.[8] F. Burkart, R. Schmidt, O. Stein, D. Wollmann, and E. Gries-mayer, “Experimental Results from the Characterization ofDiamond Particle Detectors with a High Intensity ElectronBeam”, in Proc. IPAC’14, Dresden, Germany, Jun. 2014, pp.3671–3673. doi:10.18429/JACoW-IPAC2014-THPME172[9] F. Sauli, “The gas electron multiplier (GEM): Operating prin-ciples and applications”, Nuclear Instruments and Methodsin Physics Research, Section A: Accelerators, Spectrometers,Detectors and Associated Equipment, vol. 805, pp. 2-24, 2016.doi.org/10.1016/j.nima.2015.07.060[10] T. Poikela et al., “Timepix3: A 65K channel hybrid pixelreadout chip with simultaneous ToA/ToT and sparse readout”,Journal of Instrumentation, vol. 9, no. 5, p.C05013, 2014.doi:10.1088/1748-0221/9/05/C05013[11] E. Frojdh et al., “Timepix3: First measurements and charac-terization of a hybrid-pixel detector working in event drivenmode”, Journal of Instrumentation, vol. 10, no. 1, p. C01039,2015. doi:10.1088/1748-0221/10/01/C0103913th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical ApplicationsTHPOMS0293021ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOI

   University of GroningenTesting the Properties of Beam-Dose Monitors for VHEE-FLASH Radiation TherapyBateman, J. J.; Burrows, P. N.; Dosanjh, M.; Dyks, L. A.; Korysko, P.; Corsini, R.; Farabolini,W.; Gerbershagen, A.; Heracleous, N.; Morales, S.Published in:IPAC 2022 - International Particle Accelerator Conference 2022DOI:10.18429/JACoW-IPAC2022-THPOMS029IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2022Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Bateman, J. J., Burrows, P. N., Dosanjh, M., Dyks, L. A., Korysko, P., Corsini, R., Farabolini, W.,Gerbershagen, A., Heracleous, N., Morales, S., Murtas, F., Rieker, V. F., Salvachua, B., Silari, M., &Zorloni, G. (2022). Testing the Properties of Beam-Dose Monitors for VHEE-FLASH Radiation Therapy. InIPAC 2022 - International Particle Accelerator Conference 2022 (pp. 3018-3021)https://doi.org/10.18429/JACoW-IPAC2022-THPOMS029CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 30-04-2023TESTING THE PROPERTIES OF BEAM-DOSE MONITORS FORVHEE-FLASH RADIATION THERAPYJ. J. Bateman∗, P. N. Burrows, M. Dosanjh1, L. A Dyks1, P. Korysko1,JAI, University of Oxford, Oxford, UKR. Corsini, W. Farabolini, A. Gerbershagen3, N. Heracleous, S. Morales, F. Murtas,V. F. Rieker, B. Salvachua, M. Silari, G. Zorloni, CERN, Geneva, Switzerland1also at CERN, Geneva, Switzerland2 also at PARTREC, University of Groningen, Groningen, NetherlandsAbstractVery High Energy Electrons (VHEE) of 50 - 250 MeV arean attractive choice for FLASH radiation therapy (RT). Be-fore VHEE-FLASH RT can be considered for clinical use,a reliable dosimetric and beam monitoring system needsto be developed, able to measure the dose delivered to thepatient in real-time and cut off the beam in the event of amachine fault to prevent overdosing the patient. Ionisationchambers are the standard monitors in conventional RT; how-ever, their response saturates at the high dose rates requiredfor FLASH. Therefore, a new dosimetry method is neededthat can provide reliable measurements of the delivered dosein these conditions. Experiments using 200 MeV electronswere done at the CLEAR facility at CERN to investigate theproperties of detectors such as diamond beam loss detectors,GEM foil detectors, and Timepix3 ASIC chips. From thetests, the GEM foil proved to be the most promising.INTRODUCTIONThe most widely used modality of RT is external beamtherapy with high energy photons (6 - 15 MV) and low en-ergy electrons (3 - 25 MeV). However, the maximum dosethat can be delivered to the tumour is limited by the dose thatthe surrounding healthy tissue can tolerate. This is a particu-lar challenge as these X- rays deliver their maximum dose at1.5 - 3.0 cm depth in water-equivalent tissue and then havea near-exponential attenuation. Recent research suggeststhat delivering the prescribed dose to the patient’s tumourat ultra-high dose rates (UHDR) elicits a larger differentialresponse between the tumour cells and the healthy tissues,known as the FLASH effect [1]. The entire prescribed doseis delivered within less than a second at a mean dose rate of≥ 100 Gy/s; compared to ≤ 0.03 Gy/s used in conventionalRT. Due to recent advances in particle accelerator technol-ogy such as high gradient electron acceleration cavities, e.g.the ones developed as part of the CLIC study [2], it may bepossible to treat deep-seated tumours with Very High EnergyElectrons (VHEE) with energies of 50 - 250 MeV due to theirincreased longitudinal range and sharper lateral penumbra incomparison to current clinical electron beams [3]. Ionisationchambers have been the standard for electron beam dosime-try, however, studies have shown that at the ultra high doserates required for FLASH-RT the response of the ionisation∗ joseph.bateman@physics.ox.ac.ukchamber suffers from non-linearities due to ion recombina-tion within the cavity volume [4]. Therefore, new detectorsand monitoring systems will need to be developed and testedin order to achieve accurate and reliable measurements ofthe delivered dose at UHDR for FLASH irradiations in bothpre-clinical experiments to verify the FLASH effect, and forthe eventual clinical implementation of FLASH-RT [5]. Therequirements on such a system are:• A response that does not saturate at the ultra-high doserates of ≥100 Gy/s that are required for FLASH.• A temporal resolution which is high enough to resolveindividual bunches or trains.• A response time that is fast enough to trigger a safetyinterlock in between pulses.• Minimal perturbation on the beam.The aim of the experiments described in this work is tounderstand the characteristics of the response of the detectorstested to the electron beam parameters at the CLEAR facility[6] and whether they exhibit any of the characteristics thatsuggest they would meet the criteria required for real-timedosimetry of VHEE at UHDR.PCVD DIAMOND DETECTORThe first detector tested was a B2-HV pCVD diamondbeam loss detector which is currently employed as a fastbeam loss monitor (BLM) at the LHC [7]. The diamonddetector consists of a 10 mm × 10 mm × 0.5 mm pCVDdiamond substrate coated on each side with a 200 nm thickgold electrode with a size of 8 mm × 8 mm. In the LHC, thedetector is used alongside an AD-DC splitter and a 2 GHzamplifier, however for the FLASH dosimetry experimentsonly the detector was used since the beam intensity doesnot need amplification. This detector was considered due toits known ability to have a quick response time and resolveindividual bunches when used as a BLM. However, sinceits primary usage is as a BLM and hence it is not directlyinstalled in the path of the beam center, it has been expectedthat the detector response would reach saturation at FLASHrates.SetupThe diamond detector was installed at the In-Air TestStand at CLEAR, at approximately 25 cm away from theend of the beam pipe, and was aligned such that the pCVD13th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029THPOMS029ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOI3018MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical Applicationsdiamond was on the axis of the beam. It was installed just be-hind an integrated current transformer (ICT) which was usedto measure the delivered charge. The tests on the diamonddetector were primarily to determine the beam intensities atwhich the response saturated.Results and DiscussionThe initial bias voltage for the detector was set to its nom-inal value of 500 V. The beam energy used was 200 MeV.The initial charge used was 40 pC per bunch, however for justone bunch, this was already causing the detector response tosaturate. The applied bias voltage was then adjusted downuntil the response no longer saturated which was at a voltage160 V. For the remainder of the irradiations, one bunch perpulse was used, whilst the charge per bunch was increased.Then the bias voltage was altered to a value at which thesignal no longer saturated. The results are shown in Table1. A bias voltage of 17 V was required for an unsaturatedTable 1: pCVD Diamond Detector Response SaturationValuesBunch Charge Bias Voltage at Saturation40 pC 160 V60 pC 30 V80 pC 17 Vresponse for a single bunch of 80 pC, but this led to a weaksignal with a stretched out FWHM. Furthermore, at such alow bias voltage the detector has a much lower response timeand resolving ability due to a drop in the collection efficiencyof the electrodes, hence it would not be suitable for use atsuch a low voltage [8]. Therefore, from these initial studiesit can be determined that the B2-HV pCVD Diamond BeamLoss Detector, as expected, would not be suitable as a real-time dosimeter for beam monitoring with UHDR VHEEbeams for FLASH RT. This result is in agreement with otherstudies which show this diamond detector only has a linearresponse in the range 0.01 pC - 0.06 pC [8]. For ionizingelectrons, a charge of 1 nC deposits a dose of 2 Gy in 1 cm3of water. Therefore, at the highest pulse repetition frequency(p.r.f) at CLEAR - 10 Hz [6], this equates to the diamonddetector saturating at an average dose rate of 1.6 Gy/s, sowould not be feasible for FLASH-RT.GEM FOIL DETECTORThe second detector tested was a Gas Electron Multiplier(GEM) Foil Detector. The detector consists of a thin polymerfoil, which is pierced with a high density of holes, and sand-wiched between two thin sheets of metal, clad to each face.The electric field in the pierced holes creates an avalancheof multiplied electrons upon interactions from the incomingradiation with the gas on one side of the structure, whichthen transfer to a collection region [9].SetupThe GEM foil in the detector used for this experiment hadan active area of 5 mm × 5 mm and consisted of a foil 50 𝜇mthick of kapton pierced with holes of 30 𝜇m diameter andclad with 5 𝜇m thick sheets of copper. It was positionedapproximately 40 cm away from the exit of the beam pipe atthe In-Air Test Stand of CLEAR. These tests were to deter-mine the beam intensities at which the response saturated, aswell as the detector’s resolving ability and the perturbationit has on the beam.Results and DiscussionAll of the irradiations were done at a beam energy of200 MeV. The first set of tests were with a charge of 50 pCper bunch at 1, 10, 50 and 100 bunches per train, respectively.The results showed that at these intensities the detector re-sponse does not saturate and has some temporal resolvingability on the bunches within the train. A subsequent setof irradiations was done with 100 pC per bunch with trainsof 1, 10, 50 and 100 bunches, respectively. The responseof the latter is shown in Fig. 1, and shows that at 10 nC pertrain (i.e. 100 pC per bunch with 100 bunches per train), theresponse of the GEM foil detector does not saturate. Thisequates to an average dose rate of 200 Gy/s at a 10 Hz p.r.fand therefore could be compatible with the UHDR requiredfor FLASH-RT.Figure 1: Signal detected from GEM foil with 5 mm × 5 mmactive area for 100 bunches per train and a charge of 100 pCper bunch.The temporal resolving ability of the GEM foil detectorcan be seen in Fig. 2. Here, the response of the detector tothe individual bunches can be seen (the CLEAR electronbunch spacing was 666 ps [6]).To measure the perturbation the detector had on the beam,the intensity and size of the beam was measured by a scintil-lating YAG screen 30 cm downstream of the detector, bothwith and without the detector inserted in the path of the beam.The measurements showed that the GEM foil detector scat-tered the beam to increase its size by 2.4 ×, and decreasedthe intensity of the beam by 38%.These initial results from the GEM foil detector arepromising as it shows that the response of detector doesnot saturate at charges of up to 10 nC per train. The resultsshow that the detector is also able to resolve the buncheswithin the train, and appears to have slight perturbations onthe beam.13th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical ApplicationsTHPOMS0293019ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOIFigure 2: Signal detected from GEM foil for 100 bunchesper train and a charge of 100 pC per bunch over a shortertimescale to observe resolving ability.TIMEPIX3 ASICA Timepix3 Application-Specific Integrated Circuit(ASIC) readout chip was also tested. Timepix3 is a hybridpixel detector readout chip which can record the time-of-arrival (ToA) and time-over-threshold (ToT) in each pixel[10]. The ASIC was used bare without a solid-state orgaseous sensor mounted as it was theorised that the intensi-ties from the UHDR beam required for FLASH irradiationswould be high enough to activate the readout pixels.SetupThe Timepix3 ASIC was also installed at the CLEARIn-Air Test Stand at a distance of around 50 cm from theexit of the beam pipe. The detector consists of four Timepixchips which together provide a 512 × 512 array of pixelsand a total sensitive area of 28 mm × 28 mm. The beam wastargeted onto one of the four Timepix quad chips, in whichthe response was measured. The tests were to determine thebeam intensities at which the response saturated. The mea-surements were carried out with the detector in ”Medipix”mode, in which all of the incoming particles are counted andin ToT mode, in which the incoming particles are measuredwith an incrementing counter as long as the signal is overthe threshold [11].Results and DiscussionThe response was measured for a beam energy of 200 MeVat three different beam intensities, 50 pC per train (1 bunchper train), 100 pC per train (5 bunches per train, 20 pC perbunch) and 250 pC per train (5 bunches per train, 50 pC perbunch). The response of the detector in ToT mode to the100 pC train and the 250 pC train can be seen in Fig. 3 a)and b), respectively. As can be seen in Fig. 3b), the responseof the detector already saturates at 250 pC per train, andwould hence be unsuitable for the detection of any largerintensities. This saturation was also seen at the same beamintensity when measuring the response in ”Medipix” mode.This is equivalent to an average dose rate of 5 Gy/s for a10 HZ p.r.f, therefore confirming the detector would saturateat UHDR conditions required for FLASH-RT. Whilst theresponse of the detector had saturated at these beam inten-sities, a measurement of the response of the detector afterthe experiment to no beam showed that the detector was notdamaged by the irradiations.Figure 3: Pixel intensity response of Timepix3 ASIC to: a)5 bunches of 20 pC per bunch, and b) 5 bunches of 50 pCper bunch, in ToT mode (X = Radiation Signal [a.u]).CONCLUSIONSThe aim of the experiments described in this work wasto determine whether the pCVD diamond detector, GEMfoil detector or Timepix3 ASIC exhibited the properties re-quired for real-time dosimetry for VHEE beams at UHDRrequired for FLASH RT. We concluded that neither the di-amond detector nor the Timepix3 ASIC would be suitablefor such use, since their response saturated at a charge pertrain of 80 pC and 250 pC, respectively. Considering thedose deposited in 1 cm3 of water, this corresponds to doserates of 1.6 Gy/s for the diamond detector and 5 Gy/s for theTimepix3 ASIC, demonstrating neither are able to operate atthe dose rates required for FLASH-RT. Conversely, the GEMfoil detector exhibited promising results since its responsedid not saturate at the highest charge per train used, 10 nC,which equates to a dose rate of 200 Gy/s. Hence showingthat it would be able to operate at the dose rates requiredfor FLASH-RT. Furthermore, this detector was able to showthe bunch spacing within the train, and was demonstratedto have a slight perturbation on the beam. However, furthertests would be need to be conducted on the GEM foil detectorto determine whether it’s fully suitable for use as beam-dosemonitor for FLASH RT using VHEE at UHDR, such as itsbehaviour with the larger beam sizes required for RT.REFERENCES[1] V. Favaudon et al., “Ultrahigh dose-rate FLASH irradiationincreases the differential response between normal and tu-mor tissue in mice”, Science Translational Medicine, vol. 6.,p. 245ra93, 2014. doi:10.1126/scitranslmed.3008973[2] The CLIC collaboration, the CLICdp collaboration,T. K. Charles, P. J. Giansiracusa, T. G. Lucas, R. P. Rassoolet al., “The Compact Linear 𝑒+𝑒− Collider (CLIC) - 2018Summary Report”, CERN Yellow Rep.Monogr., 2018.https://doi.org/10.48550/arXiv.1812.06018[3] C. DesRosiers et al., “150-250 MeV electron beams in radia-tion therapy”, Physics in Medicine and Biology, vol. 45, no. 7.p. 1781. 2000. doi:10.1088/0031-9155/45/7/306[4] M. McManus et al., “The challenge of ionisation chamberdosimetry in ultra-short pulsed high dose-rate Very High13th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029THPOMS029ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOI3020MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical ApplicationsEnergy Electron beams”, Scientific Reports, vol. 10, no. 1,p. 9089, 2020. doi:10.1038/s41598-020-65819-y[5] A. Vignati et al., “Beam Monitors for Tomorrow: The Chal-lenges of Electron and Photon FLASH RT”, Frontiers inPhysics, vol. 8, p. 375, 2020. doi:10.3389/fphy.2020.00375[6] K. N. Sjobak et al., “Status of the CLEAR ElectronBeam User Facility at CERN”, in Proc. IPAC’19, Mel-bourne, Australia, May 2019, pp. 983–986. doi:10.18429/JACoW-IPAC2019-MOPTS054[7] E. Griesmayer, B. Dehning, D. Dobos, E. Effinger, and H.Pernegger, “A Fast CVD Diamond Beam Loss Monitor forLHC”, in Proc. DIPAC’11, Hamburg, Germany, May 2011,paper MOPD41, pp. 143–145.[8] F. Burkart, R. Schmidt, O. Stein, D. Wollmann, and E. Gries-mayer, “Experimental Results from the Characterization ofDiamond Particle Detectors with a High Intensity ElectronBeam”, in Proc. IPAC’14, Dresden, Germany, Jun. 2014, pp.3671–3673. doi:10.18429/JACoW-IPAC2014-THPME172[9] F. Sauli, “The gas electron multiplier (GEM): Operating prin-ciples and applications”, Nuclear Instruments and Methodsin Physics Research, Section A: Accelerators, Spectrometers,Detectors and Associated Equipment, vol. 805, pp. 2-24, 2016.doi.org/10.1016/j.nima.2015.07.060[10] T. Poikela et al., “Timepix3: A 65K channel hybrid pixelreadout chip with simultaneous ToA/ToT and sparse readout”,Journal of Instrumentation, vol. 9, no. 5, p.C05013, 2014.doi:10.1088/1748-0221/9/05/C05013[11] E. Frojdh et al., “Timepix3: First measurements and charac-terization of a hybrid-pixel detector working in event drivenmode”, Journal of Instrumentation, vol. 10, no. 1, p. C01039,2015. doi:10.1088/1748-0221/10/01/C0103913th Int. Particle Acc. Conf. IPAC2022, Bangkok, Thailand JACoW PublishingISBN: 978-3-95450-227-1 ISSN: 2673-5490 doi:10.18429/JACoW-IPAC2022-THPOMS029MC8: Applications of Accelerators, Technology Transfer and Industrial RelationsU01: Medical ApplicationsTHPOMS0293021ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOI

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Testing the Properties of Beam-Dose Monitors for VHEE-FLASH Radiation Therapy

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